Journal articles on the topic 'Novel Human Protein Family'
To see the other types of publications on this topic, follow the link: Novel Human Protein Family.
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Novel Human Protein Family.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Elbadawy, Mohamed, Tatsuya Usui, Hideyuki Yamawaki, and Kazuaki Sasaki. "Novel Functions of Death-Associated Protein Kinases through Mitogen-Activated Protein Kinase-Related Signals." International Journal of Molecular Sciences 19, no. 10 (October 4, 2018): 3031. http://dx.doi.org/10.3390/ijms19103031.
Full textAbstract:
Death associated protein kinase (DAPK) is a calcium/calmodulin-regulated serine/threonine kinase; its main function is to regulate cell death. DAPK family proteins consist of DAPK1, DAPK2, DAPK3, DAPK-related apoptosis-inducing protein kinases (DRAK)-1 and DRAK-2. In this review, we discuss the roles and regulatory mechanisms of DAPK family members and their relevance to diseases. Furthermore, a special focus is given to several reports describing cross-talks between DAPKs and mitogen-activated protein kinases (MAPK) family members in various pathologies. We also discuss small molecule inhibitors of DAPKs and their potential as therapeutic targets against human diseases.
2
Davis, Beckley, Aaron Tocker, Suzanna Talento, and Kimberly Jacob. "Identification of a novel protein protein interaction pathway with NLRC3 (INM2P.359)." Journal of Immunology 194, no. 1_Supplement (May 1, 2015): 126.12. http://dx.doi.org/10.4049/jimmunol.194.supp.126.12.
Full textAbstract:
Abstract Nucleotide binding domain, leucine rich repeat CARD containing protein 3 (NLRC3) is a member of the NLR gene family. Members of this family have been associated with human inflammatory diseases such as Crohn’s disease and cryopyrin-associated periodic syndrome. Although NLRC3 (and others) are not associated with human diseases, it is expressed preferentially in the immune system and functions in pathogen recognition. NLRC3 is an intracellular protein involved in the sensing of lipopolysaccharide and cytosolic nucleic acids. NLRC3 is hypothesized to act as a negative regulator in response to bacterial and viral infection, suggesting that the vertebrate immune system has evolved specific inhibitors to limit the inflammatory response. We performed an unbiased yeast two-hybrid screen using an amino terminal fragment of NLRC3 to identify putative interacting proteins that might help elucidate the mechanism by which NLRC3 might inhibit inflammatory responses. To this end, we identified several interacting proteins. One protein in particular acts as a scaffold important in regulating the cytoskeleton, cell adhesion and proliferation. Structure function analysis has localized the domains necessary and sufficient for interacting with NLRC3. Additionally, confocal microscopy demonstrates that these two proteins colocalize in transformed human epithelial cells. This data suggests that NLRC3 interacts specifically with a novel scaffold.
3
Guignard, F., J. Mauel, and M. Markert. "Identification and characterization of a novel human neutrophil protein related to the S100 family." Biochemical Journal 309, no. 2 (July 15, 1995): 395–401. http://dx.doi.org/10.1042/bj3090395.
Full textAbstract:
A rabbit polyclonal antibody raised against myeloid-related protein 8 (MRP-8), a protein of the S100 family, recognized another S100 protein (MRP-14) as well as a protein of 6.5 kDa (p6) in the cytosol of resting neutrophils. p6 was found to be a novel member of the S100 family. It consisted of two isoforms with pI values of 6.2 (the minor form, p6a) and 6.3 (the major form, p6b) and constituted 5% of the total cytosolic proteins. Both isoforms were also demonstrated in the cytosol of monocytes, but not in lymphocytes, as previously shown for MRP-8 and MRP-14. Only the major isoform bound radioactive Ca2+, as also observed for MRP-8, whereas the different variants of MRP-14 were all labelled. On neutrophil activation with opsonized zymosan, a stimulant known to require extracellular Ca2+, 58% of p6a and 42% of p6b was translocated to the membrane. With phorbol 12-myristate 13-acetate, a Ca(2+)-independent stimulant, no translocation was detected. This translocation pattern was similar to that observed with MRP-8 and MRP-14. In addition, p6, MRP-8 and MRP-14 were specifically associated with the cytoskeletal fraction of the membrane. The Ca(2+)-dependent translocation of the novel S100 protein in parallel with MRP-8 and MRP-14 suggests a role for these proteins in regulating the Ca2+ signal to the membrane cytoskeleton and thus in regulating neutrophil activation.
4
Singh, Mahendra K., Disha Dadke, Emmanuelle Nicolas, Ilya G. Serebriiskii, Sinoula Apostolou, Adrian Canutescu, Brian L. Egleston, and Erica A. Golemis. "A Novel Cas Family Member, HEPL, Regulates FAK and Cell Spreading." Molecular Biology of the Cell 19, no. 4 (April 2008): 1627–36. http://dx.doi.org/10.1091/mbc.e07-09-0953.
Full textAbstract:
For over a decade, p130Cas/BCAR1, HEF1/NEDD9/Cas-L, and Efs/Sin have defined the Cas (Crk-associated substrate) scaffolding protein family. Cas proteins mediate integrin-dependent signals at focal adhesions, regulating cell invasion and survival; at least one family member, HEF1, regulates mitosis. We here report a previously undescribed novel branch of the Cas protein family, designated HEPL (for HEF1-Efs-p130Cas-like). The HEPL branch is evolutionarily conserved through jawed vertebrates, and HEPL is found in some species lacking other members of the Cas family. The human HEPL mRNA and protein are selectively expressed in specific primary tissues and cancer cell lines, and HEPL maintains Cas family function in localization to focal adhesions, as well as regulation of FAK activity, focal adhesion integrity, and cell spreading. It has recently been demonstrated that upregulation of HEF1 expression marks and induces metastasis, whereas high endogenous levels of p130Cas are associated with poor prognosis in breast cancer, emphasizing the clinical relevance of Cas proteins. Better understanding of the complete protein family should help inform prediction of cancer incidence and prognosis.
5
Li, Xin, Lei Chen, Chaoneng Ji, Bing Liu, Jiefeng Gu, Jian Xu, Xianqiong Zou, Shaohua Gu, and Yumin Mao. "Isolation and expression pattern of RGS21 gene, a novel RGS member." Acta Biochimica Polonica 52, no. 4 (September 8, 2005): 943–46. http://dx.doi.org/10.18388/abp.2005_3412.
Full textAbstract:
Regulators of G-protein signaling (RGS) proteins are known for the RGS domain that is composed of a conserved stretch of 120 amino acids, which binds directly to activated G-protein alpha subunits and acts as a GTPase-activating protein (GAP), leading to their deactivation and termination of downstream signals. In this study, a novel human RGS cDNA (RGS21), 1795 bp long and encoding a 152-amino acid polypeptide, was isolated by large-scale sequencing analysis of a human fetal brain cDNA library. Unlike other RGS family members, RGS21 gene has no additional domain/motif and may represent the smallest known member of RGS family. It may belong to the B/R4 subfamily, which suggests that it may serve exclusively as a negative regulator of alphai/o family members and/or alphaq/11. PCR analysis showed that RGS21 mRNA was expressed ubiquitously in the 16 tissues examined, implying general physiological roles.
6
Rakowicz-Szulczynska, Ewa M., David G. McIntosh, Peter Morris, and McClure Smith. "Novel Family of Gynecologic Cancer Antigens Detected by Anti-HIV Antibody." Infectious Diseases in Obstetrics and Gynecology 2, no. 4 (1994): 171–78. http://dx.doi.org/10.1155/s1064744994000608.
Full textAbstract:
Objective:The reactivity of gynecologic cancer proteins with monoclonal antibody (MAb) directed against the human immunodeficiency virus I (HIV-I) was tested.Methods:Cytoplasmic and nuclear proteins, extracted from a broad range of gynecologic cancers obtained during standard surgical procedures, were tested in Western blotting with MAb 5023 developed against the amino acid sequences 308–322 of the envelope protein gp120 of HIV-I.Results:Three cell membrane proteins,Mrl20,000 (p120),Mr41,000 (p41), andMr24,000 (p24), and one chromatin protein,Mr24,000 (p24), were detected by MAb 5023 in invasive, poorly differentiated cervical squamous-cell carcinoma; ovarian serous cystadenocarcinoma; poorly and well-differentiated endometrial carcinoma; vulvar squamous-cell carcinoma; and malignant mixed müllerian tumor. The same antigens were identified in cervical carcinoma cell line SiHa. Neither p120 nor p24 was recognized by other MAbs directed against the variable loop of gp120. Antigens p120 and p41 were undetectable in normal ovarian tissue and in biopsy samples of normal vaginal and rectal mucosa. Rectosigmoid cancer as well as colon carcinoma, lung carcinoma, and melanoma cell lines all tested negative.Conclusions:The identified antigens may represent either the products of human genes (proto-onc-ogenes) or, more likely, the products of an unknown virus specifically expressed in female cancer.
7
Suk, Kyoungho, Sunshin Kim, Yun-Hee Kim, Seung-Hoon Oh, Moon-Kyu Lee, Kwang-Won Kim, Hee-Dai Kim, Yeon-Soo Seo, and Myung-Shik Lee. "Identification of a novel human member of the DEAD box protein family." Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 1501, no. 1 (April 2000): 63–69. http://dx.doi.org/10.1016/s0925-4439(00)00010-7.
Full text
8
Lev, Sima, John Hernandez, Ricardo Martinez, Alon Chen, Greg Plowman, and Joseph Schlessinger. "Identification of a Novel Family of Targets of PYK2 Related to Drosophila Retinal Degeneration B (rdgB) Protein." Molecular and Cellular Biology 19, no. 3 (March 1, 1999): 2278–88. http://dx.doi.org/10.1128/mcb.19.3.2278.
Full textAbstract:
ABSTRACT The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.
9
Sellers, Robert A., David L. Robertson, and May Tassabehji. "Ancestry of the AUTS2 family–A novel group of polycomb-complex proteins involved in human neurological disease." PLOS ONE 15, no. 12 (December 11, 2020): e0232101. http://dx.doi.org/10.1371/journal.pone.0232101.
Full textAbstract:
Autism susceptibility candidate 2 (AUTS2) is a neurodevelopmental regulator associated with an autosomal dominant intellectual disability syndrome, AUTS2 syndrome, and is implicated as an important gene in human-specific evolution. AUTS2 exists as part of a tripartite gene family, the AUTS2 family, which includes two relatively undefined proteins, Fibrosin (FBRS) and Fibrosin-like protein 1 (FBRSL1). Evolutionary ancestors of AUTS2 have not been formally identified outside of the Animalia clade. A Drosophila melanogaster protein, Tay bridge, with a role in neurodevelopment, has been shown to display limited similarity to the C-terminal of AUTS2, suggesting that evolutionary ancestors of the AUTS2 family may exist within other Protostome lineages. Here we present an evolutionary analysis of the AUTS2 family, which highlights ancestral homologs of AUTS2 in multiple Protostome species, implicates AUTS2 as the closest human relative to the progenitor of the AUTS2 family, and demonstrates that Tay bridge is a divergent ortholog of the ancestral AUTS2 progenitor gene. We also define regions of high relative sequence identity, with potential functional significance, shared by the extended AUTS2 protein family. Using structural predictions coupled with sequence conservation and human variant data from 15,708 individuals, a putative domain structure for AUTS2 was produced that can be used to aid interpretation of the consequences of nucleotide variation on protein structure and function in human disease. To assess the role of AUTS2 in human-specific evolution, we recalculated allele frequencies at previously identified human derived sites using large population genome data, and show a high prevalence of ancestral alleles, suggesting that AUTS2 may not be a rapidly evolving gene, as previously thought.
10
Skeiky, Y. A., D. R. Benson, J. A. Guderian, P. R. Sleath, M. Parsons, and S. G. Reed. "Trypanosoma cruzi acidic ribosomal P protein gene family. Novel P proteins encoding unusual cross-reactive epitopes." Journal of Immunology 151, no. 10 (November 15, 1993): 5504–15. http://dx.doi.org/10.4049/jimmunol.151.10.5504.
Full textAbstract:
Abstract We have cloned and characterized cDNA molecules that encode members of the acidic ribosomal protein family (TcP proteins) from the protozoan parasite Trypanosoma cruzi. These proteins have been shown to be antigenic in individuals with T. cruzi infection. Unlike other known eukaryotic cells, T. cruzi possesses at least four types of P protein genes TcP0, TcP1, TcP2a, and TcP2b, each of which is present in multiple copies in the genome. These genes are present on at least three different chromosomes. Although the abundance of TcP0, TcP2a, and TcP2b transcripts do not appear to vary among the parasite life-cycle stages, TcP1 is predominantly expressed in the epimastigote (insect) stage. TcP0 has a C-terminal heptapeptide sequence that is similar to those of archaebacterial acidic (P-like) proteins, but the TcP1/P2 proteins terminate with a shared sequence characteristic of the P proteins of higher eukaryotes. The serine residues or other potential phosphorylation sites typically found within the highly charged C-terminal acidic domain are absent in T. cruzi P proteins. Using synthetic peptides, we demonstrated that approximately 80% of T. cruzi-infected individuals produce two distinct but cross-reactive anti-P antibody specificities directed against the C-termini of TcP0 and TcP1/P2. We also expressed the full length (non-fusion) recombinant human P0 and demonstrated that the T. cruzi anti-P antibodies cross-react with the C-terminal residues of human P-proteins. Conversely, human anti-P protein antibodies in sera from patients with SLE cross-react with the C-terminal epitope of T. cruzi TcP1/P2 proteins. The cross-reactivity of anti-TcP antibodies with human P proteins suggests that, through antigenic conservation, TcP proteins may contribute to the development of autoreactive antibodies in Chagas' disease patients.
11
Miller, M. D., S. Hata, R. De Waal Malefyt, and M. S. Krangel. "A novel polypeptide secreted by activated human T lymphocytes." Journal of Immunology 143, no. 9 (November 1, 1989): 2907–16. http://dx.doi.org/10.4049/jimmunol.143.9.2907.
Full textAbstract:
Abstract We have identified two cDNA clones, I-309 and G-26, which define genes expressed abundantly in activated human PBMC, but at low or undetectable levels in resting PBMC. Based upon nucleotide sequence analysis, both clones are predicted to encode small, structurally related polypeptides, each containing a hydrophobic leader sequence characteristic of secreted proteins and a motif of four conserved cysteine residues. Further, I-309 and G-26 are structurally related to a growing family of genes that apparently encode small polypeptides whose secretion is induced upon cell activation. I-309 represents a previously undescribed human gene. We have generated an anti-peptide antiserum to the I-309 gene product which recognizes proteins in culture supernatants of an activated T cell clone and of COS cells transfected with the I-309 cDNA, supporting the idea that I-309 encodes a secreted protein. Because I-309 encodes a small protein secreted by activated T cells that displays structural features similar to other cytokines, we believe that it defines a novel cytokine with as yet unknown function.
12
Li, Franklin, Di Zhang, and Ken Fujise. "Characterization of Fortilin, a Novel Antiapoptotic Protein." Journal of Biological Chemistry 276, no. 50 (October 11, 2001): 47542–49. http://dx.doi.org/10.1074/jbc.m108954200.
Full textAbstract:
Apoptosis is meticulously controlled in living organisms. Its dysregulation has been shown to play a key role in a number of human diseases, including neoplastic, cardiovascular, and degenerative disorders. Bcl-2 family member proteins and inhibitors of apoptosis proteins are two major negative regulators of apoptosis. We report here the characterization of novel antiapoptotic protein, fortilin, which we identified through yeast two-hybrid library screening. Sequence analysis of fortilin revealed it to be a 172-amino acid polypeptide highly conserved from mammals to plants. Fortilin is structurally unrelated to either Bcl-2 family member proteins or inhibitors of apoptosis proteins. Northern blot analysis showed the fortilin message to be ubiquitous in normal tissue but especially abundant in the liver, kidney, and small intestine. Western blot analysis using anti-fortilin antibody showed more extensive expression in cancerous cell lines (H1299, MCF-7, and A549) than in cell lines derived from normal tissue (HEK293). Immunocytochemistry using HeLa cells transiently expressing FLAG-tagged fortilin and immunohistochemistry using human breast ductal carcinoma tissue and anti-fortilin antibody both showed that fortilin is predominantly localized in the nucleus. Functionally, the transient overexpression of fortilin in HeLa cells prevented them, in a dose-dependent fashion, from undergoing etoposide-induced apoptosis. Consistently, U2OS cells stably expressing fortilin protected the cells from cell death induced by etoposide over various concentrations and durations of exposure. In addition, fortilin overexpression inhibited caspase-3-like activity as assessed by the cleavage of fluorogenic substrate benzyloxycarbonyl-DEVD-7-amido-4-(trifluoromethyl)coumarin. Furthermore, the antisense depletion of fortilin from breast cancer cell line MCF-7 was associated with massive cell death. These data suggest that fortilin represents a novel antiapoptotic protein involved in cell survival and apoptosis regulation.
13
Cusick, John K., Anusri Yanumula, Yennie Shyu, Wenjia Wang, Alyssa Abram, Jessa Alcaide, James Zhou, et al. "Hematopoietic protein RELT is upregulated in human breast and lung cancers and binds the cytoskeletal protein Filamin A." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 178.06. http://dx.doi.org/10.4049/jimmunol.208.supp.178.06.
Full textAbstract:
Abstract Receptor Expressed in Lymphoid Tissues (RELT), is a human TNFR superfamily member (TNFRSF19L) expressed most prominently in the hematopoietic system. Previous reports using RELT knockout mice indicate that RELT functions in part by inhibiting the proliferation and activation of T lymphocytes. RELT is an orphan receptor that has two homologous binding partners, RELL1 and RELL2, and collectively, these three proteins are referred to as RELT family members. This study sought to identify novel protein interactions with RELT family members and to compare the expression of RELT in normal and diseased human tissues. A yeast two-hybrid screen utilizing RELL1 as bait identified the cytoskeletal protein Filamin A (FLNA) as a prospective binding partner and physical interaction between FLNA and RELT family members was confirmed by in vitro co-immunoprecipitation. A truncated mutant of FLNA disrupts the ability of RELT family members to activate the p38 pathway and blocks the ability of RELT to induce death in human epithelial cells. Western blotting revealed endogenous RELT family members are most significantly upregulated in the breast cancer cell lines MDA-MB-231 and MCF-7, as well as the lung cancer cell line H358. Preliminary immunohistochemistry results reveal a higher intensity of RELT staining in both breast cancer and lung cancer human biopsies versus non-malignant tissue. Additionally, overexpression of RELT family members enhanced apoptosis in MDA-MB-231 and H358 cells as measured by X-gal morphology and luciferase assays. Collectively, these results further our understanding of signal transduction pathways associated with RELT family members and report the novel finding that RELT is upregulated in human breast and lung cancers. Supported by California Northstate University, College of Medicine, Seed Grant.
14
BOLLIGER, Marc F., Karl FREI, Kaspar H. WINTERHALTER, and Sergio M. GLOOR. "Identification of a novel neuroligin in humans which binds to PSD-95 and has a widespread expression." Biochemical Journal 356, no. 2 (May 24, 2001): 581–88. http://dx.doi.org/10.1042/bj3560581.
Full textAbstract:
Neuroligins, first discovered in rat brain, form a family of three synaptically enriched membrane proteins. Using reverse transcription–PCR of human brain polyadenylated RNA and extensive database searches, we identified the human homologues of the three rat neuroligins and a cDNA encoding a fourth member, which we named neuroligin 4. Neuroligin 4has 63–73% amino acid identity with the other members of the human neuroligin family, and the same predicted domain structure. DNA database analyses, furthermore, indicated that a possible fifth neuroligin gene may be present in the human genome. Northern-blot analysis revealed expression of neuroligin 4 in heart, liver, skeletal muscle and pancreas, but barely at all in brain. Overexpression of neuroligin 4 cDNA in COS-7 cells led to the production of a 110kDa protein. Immunofluorescence analysis demonstrated that the protein was integrated into the plasma membrane. Overexpression of cDNAs encoding neuroligin 4 and the PDZ-domain protein, PSD-95, in COS-7 cells resulted in the formation of detergent-resistant complexes. Neuroligin 4 did not bind to ZO-1, another PDZ-domain protein. Together, our data show that the human neuroligin family is composed of at least one additional member, and suggest that neuroligin 4 may also be produced outside the central nervous system.
15
Kawakami, T., C. Y. Pennington, and K. C. Robbins. "Isolation and oncogenic potential of a novel human src-like gene." Molecular and Cellular Biology 6, no. 12 (December 1986): 4195–201. http://dx.doi.org/10.1128/mcb.6.12.4195-4201.1986.
Full textAbstract:
We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues.
16
Kawakami, T., C. Y. Pennington, and K. C. Robbins. "Isolation and oncogenic potential of a novel human src-like gene." Molecular and Cellular Biology 6, no. 12 (December 1986): 4195–201. http://dx.doi.org/10.1128/mcb.6.12.4195.
Full textAbstract:
We have isolated cDNA molecules representing the complete coding sequence of a new human gene which is a member of the src family of oncogenes. Nucleotide sequence analysis revealed that this gene, termed slk, encoded a 537-residue protein which was 86% identical to the chicken proto-oncogene product, p60c-src, over a stretch of 191 amino acids at its carboxy terminus. In contrast, only 6% amino acid homology was observed within the amino-terminal 82 amino acid residues of these two proteins. It was possible to activate slk as a transforming gene by substituting approximately two-thirds of the slk coding sequence for an analogous region of the v-fgr onc gene present in Gardner-Rasheed feline sarcoma virus. The resulting hybrid protein molecule expressed in transformed cells demonstrated protein kinase activity with specificity for tyrosine residues.
17
Lord, Kenneth A., Caretha L. Creasy, Andrew G. King, Caroline King, Brian M. Burns, John C. Lee, and Susan B. Dillon. "REDK, a novel human regulatory erythroid kinase." Blood 95, no. 9 (May 1, 2000): 2838–46. http://dx.doi.org/10.1182/blood.v95.9.2838.009k29_2838_2846.
Full textAbstract:
We have identified a novel regulatory erythroid kinase (REDK) that is homologous to a family of dual-specificity kinases. The yeast homolog of REDK negatively regulates cell division, suggesting a similar function for REDK, which is primarily localized in the nucleus. REDK is present in hematopoietic tissues, such as bone marrow and fetal liver, but the RNA is expressed at significant levels only in erythroid or erythropoietin (EPO)-responsive cells. Two novel forms of cDNA (long and short) for REDK have been isolated that appear to be alternative splice products and imply the presence of polypeptides with differing amino termini. The ratio of short-to-long forms of REDK increases dramatically in CD34+ cells cultured with EPO, suggesting differing regulation and function for each form. REDK is predominantly found in nuclear, rather than cytoplasmic, protein extracts, and immunoprecipitated REDK is active in phosphorylating histones H2b, H3, myelin basic protein, and other coimmunoprecipitated proteins. Antisense REDK oligonucleotides promote erythroid colony formation by human bone marrow cells, without affecting colony-forming unit (CFU)-GM, CFU-G, or CFU-GEMM numbers. Maximal numbers of CFU-E and burst-forming unit–erythroid were increased, and CFU-E displayed increased sensitivity to suboptimal EPO concentrations. The data indicate that REDK acts as a brake to retard erythropoiesis.
18
Hoi, Joanne Wong Sak, Claude Lamarre, Rémi Beau, Isabelle Meneau, Adokiye Berepiki, Annick Barre, Emilia Mellado, Nick D. Read, and Jean-Paul Latgé. "A novel family of dehydrin-like proteins is involved in stress response in the human fungal pathogenAspergillus fumigatus." Molecular Biology of the Cell 22, no. 11 (June 2011): 1896–906. http://dx.doi.org/10.1091/mbc.e10-11-0914.
Full textAbstract:
During a search for genes controlling conidial dormancy in Aspergillus fumigatus, two dehydrin-like genes, DprA and DprB, were identified. The deduced proteins had repeated stretches of 23 amino acids that contained a conserved dehydrin-like protein (DPR) motif. Disrupted DprAΔ mutants were hypersensitive to oxidative stress and to phagocytic killing, whereas DprBΔ mutants were impaired in osmotic and pH stress responses. However, no effect was observed on their pathogenicity in our experimental models of invasive aspergillosis. Molecular dissection of the signaling pathways acting upstream showed that expression of DprA was dependent on the stress-activated kinase SakA and the cyclic AMP-protein kinase A (cAMP-PKA) pathways, which activate the bZIP transcription factor AtfA, while expression of DprB was dependent on the SakA mitogen-activated protein kinase (MAPK) pathway, and the zinc finger transcription factor PacC. Fluorescent protein fusions showed that both proteins were associated with peroxisomes and the cytosol. Accordingly, DprA and DprB were important for peroxisome function. Our findings reveal a novel family of stress-protective proteins in A. fumigatus and, potentially, in filamentous ascomycetes.
19
Russell, Rebecca A., Heather L. Wiegand, Michael D. Moore, Alexandra Schäfer, Myra O. McClure, and Bryan R. Cullen. "Foamy Virus Bet Proteins Function as Novel Inhibitors of the APOBEC3 Family of Innate Antiretroviral Defense Factors." Journal of Virology 79, no. 14 (July 2005): 8724–31. http://dx.doi.org/10.1128/jvi.79.14.8724-8731.2005.
Full textAbstract:
ABSTRACT Foamy viruses are a family of complex retroviruses that establish common, productive infections in a wide range of nonhuman primates. In contrast, humans appear nonpermissive for foamy virus replication, although zoonotic infections do occur. Here we have analyzed the ability of primate and mouse APOBEC3G proteins to inhibit the infectivity of primate foamy virus (PFV) virions produced in their presence. We demonstrate that several APOBEC3 proteins can potently inhibit the infectivity of a PFV-based viral vector. This inhibition correlated with the packaging of inhibitory APOBEC3 proteins into PFV virions, due to a specific PFV Gag/APOBEC3 interaction, and resulted in the G to A hypermutation of PFV reverse transcripts. While inhibition of PFV virion infectivity by primate APOBEC3 proteins was largely relieved by coexpression of the PFV Bet protein, a cytoplasmic auxiliary protein of previously uncertain function, Bet failed to relieve inhibition caused by murine APOBEC3. PFV Bet bound to human, but not mouse, APOBEC3 proteins in coexpressing cells, and this binding correlated with the specific inhibition of their incorporation into PFV virions. Of note, both PFV Bet and a second Bet protein, derived from an African green monkey foamy virus, rescued the infectivity of Vif-deficient human immunodeficiency virus type 1 (HIV-1) virions produced in the presence of African green monkey APOBEC3G and blocked the incorporation of this host factor into HIV-1 virion particles. However, neither foamy virus Bet protein reduced APOBEC3 protein expression levels in virion producer cells. While these data identify the foamy virus Bet protein as a functional ortholog of the HIV-1 Vif auxiliary protein, they also indicate that Vif and Bet block APOBEC3 protein function by distinct mechanisms.
20
KRUSE, Charli, Arnold GRÜNWELLER, Holger NOTBOHM, Sebastian KÜGLER, Werner G. PURSCHKE, and Peter K. MÜLLER. "Evidence for a novel cytoplasmic tRNA-protein complex containing the KH-multidomain protein vigilin." Biochemical Journal 320, no. 1 (November 15, 1996): 247–52. http://dx.doi.org/10.1042/bj3200247.
Full textAbstract:
Vigilin, a protein found predominantly in cells and tissues with a high biosynthetic capacity, was isolated in its native form from human HEp-2 cells (A.T.C.C. CCL23) by immunoaffinity chromatography. Vigilin forms part of a novel ribonucleoprotein complex that also contains additional, as yet uncharacterized, proteins. Experimental evidence suggests that the nucleic acids entrapped in this complex are protected from RNase and belong to the tRNA family. Using either a pool of total human RNA or radioactively labelled tRNA (tRNAAsp**) in rebinding experiments, we could show that tRNA is selectively recaptured by the RNA-depleted vigilin-containing complex.
21
POLITZ, Oliver, Alexei GRATCHEV, Peter A. G. McCOURT, Kai SCHLEDZEWSKI, Pierre GUILLOT, Sophie JOHANSSON, Gunbjorg SVINENG, et al. "Stabilin-1 and −2 constitute a novel family of fasciclin-like hyaluronan receptor homologues." Biochemical Journal 362, no. 1 (February 8, 2002): 155–64. http://dx.doi.org/10.1042/bj3620155.
Full textAbstract:
MS-1, a high-molecular-mass protein expressed by non-continuous and angiogenic endothelial cells and by alternatively activated macrophages (Mφ2), and the hepatic sinusoidal endothelial hyaluronan clearance receptor are similar with respect to tissue distribution and biochemical characteristics. In the present study we purified these proteins by immuno- and hyaluronan-affinity chromatography respectively, sequenced tryptic peptides and generated full-length cDNA sequences in both mouse and human. The novel genes, i.e. stabilin-1 and stabilin-2, code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18–20 epidermal-growth-factor domains, one X-link domain and three to six B-(X7)-B hyaluronan-binding motifs. Northern-blotting experiments revealed the presence of both stabilins in organs with predominant endothelial sinuses such as liver, spleen and lymph node: stabilin-1 mRNA was also detected in organs with predominant Mφ2 cells, such as placenta, and in interleukin-4/glucocorticoid-stimulated Mφ2 cells in vitro. A polyclonal antibody made against human recombinant stabilin-1 confirmed the expression of stabilin-1 protein in splenic sinus endothelial cells in vivo and in Mφ2 in vitro. On the basis of high similarity at the protein level and the unique domain composition, which differs from that of all other known fasciclin-like proteins and hyaluronan receptors, stabilin-1 and stabilin-2 define a novel family of fasciclin-like hyaluronan receptor homologues that might play a role in cell—cell and cell—matrix interactions in vascular function and inflammatory processes.
22
Ilhan, Aysegul, Wolfgang Gartner, Anastasiya Nabokikh, Teodora Daneva, Otto Majdic, Gerald Cohen, Georg A. Böhmig, Wolfgang Base, Walter H. Hörl, and Ludwig Wagner. "Localization and characterization of the novel protein encoded by C20orf3." Biochemical Journal 414, no. 3 (August 27, 2008): 485–95. http://dx.doi.org/10.1042/bj20080503.
Full textAbstract:
In the present study, we characterized the gene product of open reading frame 3 encoded at human chromosome 20 (C20orf3), which represents a member of the lactonohydrolase super family. Multiple-tissue Northern blot analysis showed ubiquitous expression of the 2.4 kb transcript coding for 416 amino acids, with highest levels in human liver, placenta and kidney. After recombinant production of protein variants in Escherichia coli and insect cells, antibodies directed against different epitopes within the C20orf3 gene product were generated. Using these immunoreagents, protein expression was demonstrated in the liver, and glomerular and tubular structures of the kidney, as well as in endothelial cells and arterial wall. Positive staining was also observed at the pancreatic islets of Langerhans. Using immunoblotting, we identified three size variants. In line with the results of in silico analysis demonstrating a single transmembrane sequence (amino acids 40–61) at the N-terminus of the full-length protein, FACS cell-surface staining confirmed a mainly extracellular localization of the full-length protein. Sucrose density gradient cell fractionation revealed membrane association of the dominant 50 kDa variant in HepG2 and Rin-5F cells. The finding of a strong arylesterase activity with β-naphthyl acetate and phenyl acetate of the C20orf3 protein-containing fractions suggests potential involvement of this protein in enzymatic processes. C20orf3 promoter-driven reporter assays, which were verified by gene-specific RT-qPCR (real-time quantitative PCR) showed a strong inhibitory effect of human serum on transcription using the HEK-293 human embryonic kidney cell line. In conclusion, we characterized the structure and expression pattern of the C20orf3 gene product. According to a series of analogies with PON (paraoxonase) family members, we speculate that the C20orf3 gene product represents a new member of this important protein family present at the cellular level.
23
Carr, C. S., and P. A. Sharp. "A helix-loop-helix protein related to the immunoglobulin E box-binding proteins." Molecular and Cellular Biology 10, no. 8 (August 1990): 4384–88. http://dx.doi.org/10.1128/mcb.10.8.4384-4388.1990.
Full textAbstract:
A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.
24
Carr, C. S., and P. A. Sharp. "A helix-loop-helix protein related to the immunoglobulin E box-binding proteins." Molecular and Cellular Biology 10, no. 8 (August 1990): 4384–88. http://dx.doi.org/10.1128/mcb.10.8.4384.
Full textAbstract:
A human cDNA encoding a novel protein in the helix-loop-helix family has been isolated by screening a bacteriophage expression library with a probe containing the binding site for major late transcription factor. The protein encoded by this cDNA, TFEB, probably recognizes E-box sequences in the heavy-chain immunoglobulin enhancer.
25
Baldwin, Stephen A., Sylvia Y. M. Yao, Ralph J. Hyde, Amy M. L. Ng, Sophie Foppolo, Kay Barnes, Mabel W. L. Ritzel, Carol E. Cass, and James D. Young. "Functional Characterization of Novel Human and Mouse Equilibrative Nucleoside Transporters (hENT3 and mENT3) Located in Intracellular Membranes." Journal of Biological Chemistry 280, no. 16 (February 8, 2005): 15880–87. http://dx.doi.org/10.1074/jbc.m414337200.
Full textAbstract:
The first mammalian examples of the equilibrative nucleoside transporter family to be characterized, hENT1 and hENT2, were passive transporters located predominantly in the plasma membranes of human cells. We now report the functional characterization of members of a third subgroup of the family, from human and mouse, which differ profoundly in their properties from previously characterized mammalian nucleoside transporters. The 475-residue human and mouse proteins, designated hENT3 and mENT3, respectively, are 73% identical in amino acid sequence and possess long N-terminal hydrophilic domains that bear typical (DE)XXXL(LI) endosomal/lysosomal targeting motifs. ENT3 transcripts and proteins are widely distributed in human and rodent tissues, with a particular abundance in placenta. However, in contrast to ENT1 and ENT2, the endogenous and green fluorescent protein-tagged forms of the full-length hENT3 protein were found to be predominantly intracellular proteins that co-localized, in part, with lysosomal markers in cultured human cells. Truncation of the hydrophilic N-terminal region or mutation of its dileucine motif to alanine caused the protein to be relocated to the cell surface both in human cells and inXenopusoocytes, allowing characterization of its transport activity in the latter. The protein proved to be a broad selectivity, low affinity nucleoside transporter that could also transport adenine. Transport activity was relatively insensitive to the classical nucleoside transport inhibitors nitrobenzylthioinosine, dipyridamole, and dilazep and was sodium ion-independent. However, it was strongly dependent upon pH, and the optimum pH value of 5.5 probably reflected the location of the transporter in acidic, intracellular compartments.
26
Callahan, Michael A., Mark A. Handley, Yung-Hui Lee, Katrin J. Talbot, J. Wade Harper, and Antonito T. Panganiban. "Functional Interaction of Human Immunodeficiency Virus Type 1 Vpu and Gag with a Novel Member of the Tetratricopeptide Repeat Protein Family." Journal of Virology 72, no. 6 (June 1, 1998): 5189–97. http://dx.doi.org/10.1128/jvi.72.6.5189-5197.1998.
Full textAbstract:
ABSTRACT Viral protein U (Vpu) is a protein encoded by human immunodeficiency virus type 1 (HIV-1) that promotes the degradation of the virus receptor, CD4, and enhances the release of virus particles from cells. We isolated a cDNA that encodes a novel cellular protein that interacts with Vpu in vitro, in vivo, and in yeast cells. This Vpu-binding protein (UBP) has a molecular mass of 41 kDa and is expressed ubiquitously in human tissues at the RNA level. UBP is a novel member of the tetratricopeptide repeat (TPR) protein family containing four copies of the 34-amino-acid TPR motif. Other proteins that contain TPR motifs include members of the immunophilin superfamily, organelle-targeting proteins, and a protein phosphatase. UBP also interacts directly with HIV-1 Gag protein, the principal structural component of the viral capsid. However, when Vpu and Gag are coexpressed, stable interaction between UBP and Gag is diminished. Furthermore, overexpression of UBP in virus-producing cells resulted in a significant reduction in HIV-1 virion release. Taken together, these data indicate that UBP plays a role in Vpu-mediated enhancement of particle release.
27
Cottage, Amanda, Yvonne J. K. Edwards, and Greg Elgar. "SAND, a New Protein Family: From Nucleic Acid to Protein Structure and Function Prediction." Comparative and Functional Genomics 2, no. 4 (2001): 226–35. http://dx.doi.org/10.1002/cfg.93.
Full textAbstract:
As a result of genome, EST and cDNA sequencing projects, there are huge numbers of predicted and/or partially characterised protein sequences compared with a relatively small number of proteins with experimentally determined function and structure. Thus, there is a considerable attention focused on the accurate prediction of gene function and structure from sequence by using bioinformatics. In the course of our analysis of genomic sequence fromFugu rubripes, we identified a novel gene,SAND, with significant sequence identity to hypothetical proteins predicted inSaccharomyces cerevisiae, Schizosaccharomyces pombe, Caenorhabditis elegans, aDrosophila melanogastergene, and mouse and human cDNAs. Here we identify a furtherSANDhomologue in human andArabidopsis thalianaby use of standard computational tools. We describe the genomic organisation ofSANDin these evolutionarily divergent species and identify sequence homologues from EST database searches confirming the expression of SAND in over 20 different eukaryotes. We confirm the expression of two different SAND paralogues in mammals and determine expression of one SAND in other vertebrates and eukaryotes. Furthermore, we predict structural properties of SAND, and characterise conserved sequence motifs in this protein family.
28
Zitzer, Heike, Hans-Hinrich Hönck, Dietmar Bächner, Dietmar Richter, and Hans-Jürgen Kreienkamp. "Somatostatin Receptor Interacting Protein Defines a Novel Family of Multidomain Proteins Present in Human and Rodent Brain." Journal of Biological Chemistry 274, no. 46 (November 12, 1999): 32997–3001. http://dx.doi.org/10.1074/jbc.274.46.32997.
Full text
29
Foster, R., K. Q. Hu, Y. Lu, K. M. Nolan, J. Thissen, and J. Settleman. "Identification of a novel human Rho protein with unusual properties: GTPase deficiency and in vivo farnesylation." Molecular and Cellular Biology 16, no. 6 (June 1996): 2689–99. http://dx.doi.org/10.1128/mcb.16.6.2689.
Full textAbstract:
We have identified a human Rho protein, RhoE, which has unusual structural and biochemical properties that suggest a novel mechanism of regulation. Within a region that is highly conserved among small GTPases, RhoE contains amino acid differences specifically at three positions that confer oncogenicity to Ras (12, 59, and 61). As predicted by these substitutions, which impair GTP hydrolysis in Ras, RhoE binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Replacing all three positions in RhoE with conventional amino acids completely restores GTPase activity. In vivo, RhoE is found exclusively in the GTP-bound form, suggesting that unlike previously characterized small GTPases, RhoE may be normally maintained in an activated state. Thus, amino acid changes in Ras that are selected during tumorigenesis have evolved naturally in this Rho protein and have similar consequences for catalytic function. All previously described Rho family proteins are modified by geranylgeranylation, a lipid attachment required for proper membrane localization. In contrast, the carboxy-terminal sequence of RhoE predicts that, like Ras proteins, RhoE is normally farnesylated. Indeed, we have found that RhoE in farnesylated in vivo and that this modification is required for association with the plasma membrane and with an unidentified cellular structure that may play a role in adhesion. Thus, two unusual structural features of this novel Rho protein suggest a striking evolutionary divergence from the Rho family of GTPases.
30
Mullins, John J., Linda J. Mullins, Donald R. Dunbar, William J. Brammar, Kenneth W. Gross, and Steven D. Morley. "Identification of a human ortholog of the mouse Dcpp gene locus, encoding a novel member of the CSP-1/Dcpp salivary protein family." Physiological Genomics 28, no. 1 (December 2006): 129–40. http://dx.doi.org/10.1152/physiolgenomics.00153.2006.
Full textAbstract:
Salivary fluid, the collective product of numerous major and minor salivary glands, contains a range of secretory proteins that play key defensive, digestive, and gustatory roles in the oral cavity. To understand the distinct protein “signature” contributed by individual salivary glands to salivary secretions, we studied a family of proteins shown by in vitro mRNA translation to be abundantly expressed in mouse sublingual glands. Molecular cloning, Southern blotting, and restriction fragment length polymorphism analyses showed these to represent one known and two novel members of the common salivary protein (CSP-1)/Demilune cell and parotid protein (Dcpp) salivary protein family, the genes for which are closely linked in the T-complex region of mouse chromosome 17. Bioinformatic analysis identified a putative human CSP-1/Dcpp ortholog, HRPE773, expressed predominantly in human salivary tissue, that shows 31% amino acid identity and 45% amino acid similarity to the mouse Dcpp query sequence. The corresponding human gene displays a similar structure to the mouse Dcpp genes and is located on human chromosome 16 in a region known to be syntenic with the T-complex region of mouse chromosome 17. The predicted mouse and human proteins both display classical NH2-terminal signal sequences, putative jacalin-related lectin domains, and potential N-linked glycosylation sites, suggesting secretion via sublingual saliva into the oral cavity where they may display antimicrobial activity or provide a defensive coating to enamel. Identification of a human CSP-1/Dcpp ortholog therefore provides a key tool for investigation of salivary protein function in human oral health and disease.
31
Opo, F. A. Dain Md, Saleh Alkarim, Ghadeer I. Alrefaei, Mohammad Habibur Rahman Molla, Nouf H. Alsubhi, Faisal Alzahrani, and Foysal Ahammad. "Pharmacophore-Model-Based Virtual-Screening Approaches Identified Novel Natural Molecular Candidates for Treating Human Neuroblastoma." Current Issues in Molecular Biology 44, no. 10 (October 13, 2022): 4838–58. http://dx.doi.org/10.3390/cimb44100329.
Full textAbstract:
The mortality of cancer patients with neuroblastoma is increasing due to the limited availability of specific treatment options. Few drug candidates for combating neuroblastoma have been developed, and identifying novel therapeutic candidates against the disease is an urgent issue. It has been found that muc-N protein is amplified in one-third of human neuroblastomas and expressed as an attractive drug target against the disease. The myc-N protein interferes with the bromodomain and extraterminal (BET) family proteins. Pharmacologically inhibition of the protein potently depletes MYCN in neuroblastoma cells. BET inhibitors target MYCN transcription and show therapeutic efficacy against neuroblastoma. Therefore, the study aimed to identify potential inhibitors against the BET family protein, specifically Brd4 (brodamine-containing protein 4), to hinder the activity of neuroblastoma cells. To identify effective molecular candidates against the disease, a structure-based pharmacophore model was created for the binding site of the Brd4 protein. The pharmacophore model generated from the protein Brd4 was validated to screen potential natural active compounds. The compounds identified through the pharmacophore-model-based virtual-screening process were further screened through molecular docking, ADME (absorption, distribution, metabolism, and excretion), toxicity, and molecular dynamics (MD) simulation approach. The pharmacophore-model-based screening process initially identified 136 compounds, further evaluated based on molecular docking, ADME analysis, and toxicity approaches, identifying four compounds with good binding affinity and lower side effects. The stability of the selected compounds was also confirmed by dynamic simulation and molecular mechanics with generalized Born and surface area solvation (MM-GBSA) methods. Finally, the study identified four natural lead compounds, ZINC2509501, ZINC2566088, ZINC1615112, and ZINC4104882, that will potentially inhibit the activity of the desired protein and help to fight against neuroblastoma and related diseases. However, further evaluations through in vitro and in vivo assays are suggested to identify their efficacy against the desired protein and disease.
32
Davis, Beckley K., Elisabeth Chapman, Kalida Gawon, Izzy Petrecca, Taylor Baker, and Alma Rechnitzer. "NLRC3 Localizes to the Endoplasmic Reticulum via Interactions with a Novel ER-Resident Protein." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 52.01. http://dx.doi.org/10.4049/jimmunol.208.supp.52.01.
Full textAbstract:
Abstract Nucleotide binding domain, leucine rich repeat CARD containing protein 3 (NLRC3) is a member of the NLR gene family. Members of this family have been associated with human inflammatory diseases such as Crohn’s disease and cryopyrin-associated periodic syndrome. Although NLRC3 (and others) are not associated with human diseases, it is expressed preferentially in the immune system and functions in pathogen recognition. NLRC3 is an intracellular protein involved in the sensing of lipopolysaccharide and cytosolic nucleic acids. NLRC3 is hypothesized to act as a negative regulator in response to bacterial and viral infection, suggesting that the vertebrate immune system has evolved specific inhibitors to limit the inflammatory response. We performed an unbiased yeast two-hybrid screen using an amino terminal fragment of NLRC3 to identify putative interacting proteins that might help elucidate the mechanism by which NLRC3 might inhibit inflammatory responses. To this end, we identified several interacting proteins. One protein in particular localizes to the endoplasmic reticulum (ER) and might serve as a localization-dependent anchor for NLRC3, thus facilitating its interaction with STING and TBK1. Here we show NLRC3 is distributed to the ER where it can interact with several important signaling molecules involved in type I interferon production. Supported by a grant from the NIH (R15 GM134430)
33
Selbie, Lisa A., Andrea Townsend-Nicholson, Tiina P. Iismaa, and John Shine. "Novel G protein-coupled receptors: a gene family of putative human olfactory receptor sequences." Molecular Brain Research 13, no. 1-2 (March 1992): 159–63. http://dx.doi.org/10.1016/0169-328x(92)90057-i.
Full text
34
Arai, Shigeki, Akio Matsushita, Kun Du, Ken Yagi, Yasushi Okazaki, and Riki Kurokawa. "Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9." FEBS Letters 581, no. 29 (November 20, 2007): 5649–57. http://dx.doi.org/10.1016/j.febslet.2007.11.022.
Full text
35
Zhang, Xiaoping, Changjiang Weng, Yuan Li, Xiaoyan Wang, Chunsun Jiang, Xuemei Li, Youli Xu, Quan Chen, Lei Pan, and Hong Tang. "Human Bop is a novel BH3-only member of the Bcl-2 protein family." Protein & Cell 3, no. 10 (October 2012): 790–801. http://dx.doi.org/10.1007/s13238-012-2069-7.
Full text
36
Soret, Johann, Renata Gattoni, Cécile Guyon, Alain Sureau, Michel Popielarz, Erwann Le Rouzic, Stéphanie Dumon, et al. "Characterization of SRp46, a Novel Human SR Splicing Factor Encoded by a PR264/SC35 Retropseudogene." Molecular and Cellular Biology 18, no. 8 (August 1, 1998): 4924–34. http://dx.doi.org/10.1128/mcb.18.8.4924.
Full textAbstract:
ABSTRACT The highly conserved SR family contains a growing number of phosphoproteins acting as both essential and alternative splicing factors. In this study, we have cloned human genomic and cDNA sequences encoding a novel SR protein designated SRp46. Nucleotide sequence analyses have revealed that the SRp46 gene corresponds to an expressed PR264/SC35 retropseudogene. As a result of mutations and amplifications, the SRp46 protein significantly differs from the PR264/SC35 factor, mainly at the level of its RS domain. Northern and Western blot analyses have established that SRp46 sequences are expressed at different levels in several human cell lines and normal tissues, as well as in simian cells. In contrast, sequences homologous to SRp46 are not present in mice. In vitro splicing studies indicate that the human SRp46 recombinant protein functions as an essential splicing factor in complementing a HeLa cell S100 extract deficient in SR proteins. In addition, complementation analyses performed with β-globin or adenovirus E1A transcripts and different splicing-deficient extracts have revealed that SRp46 does not display the same activity as PR264/SC35. These results demonstrate, for the first time, that an SR splicing factor, which represents a novel member of the SR family, is encoded by a functional retropseudogene.
37
Teahan, C. G., N. F. Totty, and A. W. Segal. "Isolation and characterization of grancalcin, a novel 28 kDa EF-hand calcium-binding protein from human neutrophils." Biochemical Journal 286, no. 2 (September 1, 1992): 549–54. http://dx.doi.org/10.1042/bj2860549.
Full textAbstract:
A novel 28 kDa protein, which we have named ‘grancalcin’, has been identified in human neutrophils. The protein was isolated from the cytosol and found to be a homodimer, with an apparent molecular mass of 55 kDa on gel filtration. Polyclonal antibodies were raised to the native protein. N-Terminal sequence analysis and tryptic-peptide sequence analysis was performed. The protein exhibits sequence similarity to sorcin, a 24 kDa calcium-binding protein over-expressed in certain multi-drug-resistant cell lines. It appears to be a member of the EF-hand family of calcium-binding proteins. The association of a high proportion of this protein with the membranes and granules in the presence of physiological concentrations of calcium may indicate a role in granule-membrane fusion and degranulation.
38
Morgan-Spencer, Alex, and Daniel Greenberg. "P-REX1: A Novel RAC Activing Guanine-Nucleotide Exchange Factor in Human Platelets." Blood 110, no. 11 (November 16, 2007): 3639. http://dx.doi.org/10.1182/blood.v110.11.3639.3639.
Full textAbstract:
Abstract A major signaling pathway that regulates platelet shape change and reorganization of the cytoskeleton involves the Rho family of GTPases whose members include Rac, CDC42 and RhoA. These GTPases are converted from their inactive or GDP-loaded state to the active or GTP-loaded state by a class of enzymes called Guanine-nucleotide Exchange Factors (GEFs). GEFs are a family of multi-domain proteins that contain a GDP-GTP exchange domain (DH-PH) as well as other protein interacting domains that are regulated by the activation of receptors present on the platelet surface. We used an affinity binding technique followed by mass spectrometry analysis to identify novel Rac binding GEFs from platelet lysates. Recombinant GST-Rac fusion proteins bound to agarose beads were prepared in the GTP, GDP and nucleotide-free states and incubated with human platelet lysates. Platelet lysate proteins associated with the different GST-Rac preparations (GTP-bound, GDP-bound or nucleotide-free) were eluted and run on SDS-PAGE. Gel slices were then cut out, trypsin digested and analyzed by mass spectrometry. Platelet GEFs were identified by the presence of a DH-PH domain. Using this technique we identified three novel Rac-associated platelet GEFs including P-REX1, a G-βγ protein and phosphatidylinositol (3,4,5)-triphosphate regulated GEF previously found in neutrophils and neurons (Welch, H.C.E et al., Cell108;809–822, 2002). PREX-1 is a 196kDa peptide composed of 1659 amino that specifically activates Rac in neutrophils. In addition to the DH-PH exchange domain, PREX-1 also contains tandem PDZ and DEP domains as well as significant similarity over its C-terminal half to Inositol Polyphosphate 4-Phosphatase. Western analysis with anti-P-REX1 antibody (gift of H.C. Welch, Barbraham Institute, U.K.) showed that PREX-1 is present in purified whole platelet lysates. We have also shown that platelet PREX-1 specifically associates with GST-Rac by affinity pull-down experiments. Functional studies to characterize the exchange activity of platelet PREX-1 are ongoing. PREX-1 is the only known GEF that is directly regulated by G-βγ protein (Hill, K. et al., J Biol Chem280(6):4166–4173, 2005) and represents a novel pathway for platelet G protein coupled receptor signaling through Rac in human platelets.
39
Funayama, N., A. Nagafuchi, N. Sato, S. Tsukita, and S. Tsukita. "Radixin is a novel member of the band 4.1 family." Journal of Cell Biology 115, no. 4 (November 15, 1991): 1039–48. http://dx.doi.org/10.1083/jcb.115.4.1039.
Full textAbstract:
Radixin is an actin barbed-end capping protein which is highly concentrated in the undercoat of the cell-to-cell adherens junction and the cleavage furrow in the interphase and mitotic phase, respectively (Tsukita, Sa., Y. Hieda, and Sh. Tsukita. 1989 a.J. Cell Biol. 108:2369-2382; Sato, N., S. Yonemura, T. Obinata, Sa. Tsukita, and Sh. Tsukita. 1991. J. Cell Biol. 113:321-330). To further understand the structure and functions of the radixin molecule, we isolated and sequenced the cDNA clones encoding mouse radixin. Direct peptide sequencing of radixin and immunological analysis with antiserum to a fusion protein were performed to confirm that the protein encoded by these clones is identical to radixin. The composite cDNA is 4,241 nucleotides long and codes for a 583-amino acid polypeptide with a calculated molecular mass of 68.5 kD. Sequence analysis has demonstrated that mouse radixin shares 75.3% identity with human ezrin, which was reported to be a member of the band 4.1 family. We then isolated the cDNA encoding mouse ezrin. Sequence analysis and Northern blot analysis revealed that radixin and ezrin are similar but distinct (74.9% identity), leading us to conclude that radixin is a novel member of the band 4.1 family. In erythrocytes the band 4.1 protein acts as a key protein in the association of short actin filaments with a plasma membrane protein (glycophorin), together with spectrin. Therefore, the sequence similarity between radixin and band 4.1 protein described in this study favors the idea that radixin plays a crucial role in the association of the barbed ends of actin filaments with the plasma membrane in the cell-to-cell adherens junction and the cleavage furrow.
40
Knott, Gavin, Mihwa Lee, Daniel Passon, Agata Sadowska, Archa Fox, Maria Conte, and Charles Bond. "Structure and dynamics of the DBHS protein family members SFPQ, NONO and PSPC1." Acta Crystallographica Section A Foundations and Advances 70, a1 (August 5, 2014): C1655. http://dx.doi.org/10.1107/s2053273314083442.
Full textAbstract:
The Drosophila behaviour/human splicing (DBHS) proteins are a family of obligatory dimeric proteins found in higher order mammals down to the simplest invertebrates. `Multifunctional protein family' essentially captures what is understood regarding DBHS protein function where they are cited to regulate transcriptional initiation, the processing and export of RNA, maintenance of genomic DNA, nuclear pH homeostasis and carcinogenesis [1]. Furthermore, with roles in binding a diverse range of RNAs and both single and double stranded DNA, it is difficult to establish a coherent picture for their nuclear activities. In humans, the family consists of three highly conserved members, namely Non-POU domain-containing octamer-binding protein (NONO/p54nrb), splicing factor proline/glutamine rich (SFPQ/PSF) and paraspeckle protein component 1 (PSPC1). The conserved DBHS region of these proteins comprises tandem RNA recognition motifs (RRMs), a NOPS domain and a C-terminal coiled-coil domain. The unique structural arrangement of these domains facilitates an intimate dimerisation interface that gives rise to a novel arrangement of RRMs [2]. Given this interface, it is not surprising that DBHS proteins likely exist as either homo- or heterodimers in vivo. Here we report the first structure of the ancestral C. elegans DBHS protein, NONO-1, refined to 2.8 Å. The structure clearly illustrates the consistent obligatory nature of DBHS dimerisation and through isothermal titration calorimetry we have demonstrated that human DBHS proteins prefer a heterodimeric state in vitro. There is a growing appreciation for the fundamental significance of DBHS proteins in human health and disease and this work highlights the critical need for a more robust assessment of in vivo DBHS function.
41
Edwards, John C. "A novel p64-related Cl−channel: subcellular distribution and nephron segment-specific expression." American Journal of Physiology-Renal Physiology 276, no. 3 (March 1, 1999): F398—F408. http://dx.doi.org/10.1152/ajprenal.1999.276.3.f398.
Full textAbstract:
Several closely related proteins that have been implicated as chloride channels of intracellular membranes have recently been described. We report here the molecular cloning and characterization of a new member of this family from human cells. On the basis of sequence similarity, we conclude that this new protein represents the human version of a previously described protein from rat brain named p64H1. The human version of p64H1 (huH1) is a 28.7-kDa protein that shows an apparent molecular mass of 31 kDa by SDS-PAGE. A single 4.5-kb message is detected on Northern blots and is present in all tissues probed. The protein is expressed in an intracellular vesicular pattern in Panc-1 cells that is distinct from the endoplasmic reticulum, fluid-phase endocytic, and transferrin-recycling compartments, but which does colocalize with caveolin. In human kidney, huH1 is highly expressed in a diffuse pattern in the apical domain of proximal tubule cells. huH1 is expressed less abundantly in a vesicular pattern in glomeruli and distal nephron.
42
Csépányi-Kömi, Roland, Gábor Sirokmány, Miklós Geiszt, and Erzsébet Ligeti. "ARHGAP25, a novel Rac GTPase-activating protein, regulates phagocytosis in human neutrophilic granulocytes." Blood 119, no. 2 (January 12, 2012): 573–82. http://dx.doi.org/10.1182/blood-2010-12-324053.
Full textAbstract:
Members of the Rac/Rho family of small GTPases play an essential role in phagocytic cells in organization of the actin cytoskeleton and production of toxic oxygen compounds. GTPase-activating proteins (GAPs) decrease the amount of the GTP-bound active form of small GTPases, and contribute to the control of biologic signals. The number of potential Rac/RhoGAPs largely exceeds the number of Rac/Rho GTPases and the expression profile, and their specific role in different cell types is largely unknown. In this study, we report for the first time the properties of full-length ARHGAP25 protein, and show that it is specifically expressed in hematopoietic cells, and acts as a RacGAP both in vitro and in vivo. By silencing and overexpressing the protein in neutrophil model cell lines (PLB-985 and CosPhoxFcγR, respectively) and in primary macrophages, we demonstrate that ARHGAP25 is a negative regulator of phagocytosis acting probably via modulation of the actin cytoskeleton.
43
Rollins, B. J., P. Stier, T. Ernst, and G. G. Wong. "The human homolog of the JE gene encodes a monocyte secretory protein." Molecular and Cellular Biology 9, no. 11 (November 1989): 4687–95. http://dx.doi.org/10.1128/mcb.9.11.4687-4695.1989.
Full textAbstract:
The mouse fibroblast gene, JE, was one of the first platelet-derived growth factor-inducible genes to be described as such. The protein encoded by JE (mJE) is the prototype of a large family of secreted, cytokinelike glycoproteins, all of whose members are induced by a mitogenic or activation signal in monocytes macrophages, and T lymphocytes; JE is the only member to have been identified in fibroblasts. We report the identification of a human homolog for murine JE, cloned from human fibroblasts. The protein predicted by the coding sequence of human JE (hJE) is 55 amino acids shorter than mJE, and its sequence is identical to that of a recently purified monocyte chemoattractant. When expressed in COS cells, the human JE cDNA directed the secretion of N-glycosylated proteins of Mr 16,000 to 18,000 as well as proteins of Mr 15,500, 15,000, and 13,000. Antibodies raised against mJE recognized these hJE species, all of which were secreted by human fibroblasts. hJE expression was stimulated in HL60 cells during phorbol myristate acetate-induced monocytoid differentiation. However, resting human monocytes constitutively secreted hJE; treatment with gamma interferon did not enhance hJE expression in monocytes, and treatment with phorbol myristate acetate or lipopolysaccharide inhibited its expression. Thus, human JE encodes yet another member of the large family of JE-related cytokinelike proteins, in this case a novel human monocyte and fibroblast secretory protein.
44
Rollins, B. J., P. Stier, T. Ernst, and G. G. Wong. "The human homolog of the JE gene encodes a monocyte secretory protein." Molecular and Cellular Biology 9, no. 11 (November 1989): 4687–95. http://dx.doi.org/10.1128/mcb.9.11.4687.
Full textAbstract:
The mouse fibroblast gene, JE, was one of the first platelet-derived growth factor-inducible genes to be described as such. The protein encoded by JE (mJE) is the prototype of a large family of secreted, cytokinelike glycoproteins, all of whose members are induced by a mitogenic or activation signal in monocytes macrophages, and T lymphocytes; JE is the only member to have been identified in fibroblasts. We report the identification of a human homolog for murine JE, cloned from human fibroblasts. The protein predicted by the coding sequence of human JE (hJE) is 55 amino acids shorter than mJE, and its sequence is identical to that of a recently purified monocyte chemoattractant. When expressed in COS cells, the human JE cDNA directed the secretion of N-glycosylated proteins of Mr 16,000 to 18,000 as well as proteins of Mr 15,500, 15,000, and 13,000. Antibodies raised against mJE recognized these hJE species, all of which were secreted by human fibroblasts. hJE expression was stimulated in HL60 cells during phorbol myristate acetate-induced monocytoid differentiation. However, resting human monocytes constitutively secreted hJE; treatment with gamma interferon did not enhance hJE expression in monocytes, and treatment with phorbol myristate acetate or lipopolysaccharide inhibited its expression. Thus, human JE encodes yet another member of the large family of JE-related cytokinelike proteins, in this case a novel human monocyte and fibroblast secretory protein.
45
Zhu, A. X., Y. Zhao, D. E. Moller, and J. S. Flier. "Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3." Molecular and Cellular Biology 14, no. 12 (December 1994): 8202–11. http://dx.doi.org/10.1128/mcb.14.12.8202-8211.1994.
Full textAbstract:
Mitogen-activated protein kinases, or extracellular signal-regulated kinases (ERKs), are serine/threonine protein kinases that are activated in response to a wide variety of extracellular stimuli and are encoded by a multigene family. Little is known about the function of the ERK-3 subfamily. To explore the molecular diversity of the ERK-3 subfamily, we isolated a novel human cDNA, designated Hu-ERK-3, from a fetal skeletal muscle library. Analysis of the complete 3,920-bp nucleotide sequence revealed that this clone encodes a predicted protein of 721 amino acids. In vitro transcription-translation generates a 97-kDa protein referred to as p97MAPK. Of all of the sequences compared, p97MAPK is the most homologous to rat ERK-3. Interestingly, although p97MAPK is highly (98%) homologous to ERK-3 at the amino acid level within the N-terminal two-thirds of the coding region, it diverges at the carboxyl terminus as a result of a unique extension of 178 amino acids. Although expression of p97MAPK was detected in all of the tissues tested by Northern (RNA) analysis, the most abundant expression was seen in skeletal muscle. An antibody raised against the unique C terminus recognized a 97-kDa protein in human cells. By using this antibody in an immune complex protein kinase assay, we have shown that treatment of human fibroblasts with serum or phorbol esters activates a myelin basic protein and histone H1 kinase activity in immunoprecipitates. p97MAPK appears to be the human homolog of rat ERK-3, and a member of this family is an active protein kinase.
46
Zhu, A. X., Y. Zhao, D. E. Moller, and J. S. Flier. "Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3." Molecular and Cellular Biology 14, no. 12 (December 1994): 8202–11. http://dx.doi.org/10.1128/mcb.14.12.8202.
Full textAbstract:
Mitogen-activated protein kinases, or extracellular signal-regulated kinases (ERKs), are serine/threonine protein kinases that are activated in response to a wide variety of extracellular stimuli and are encoded by a multigene family. Little is known about the function of the ERK-3 subfamily. To explore the molecular diversity of the ERK-3 subfamily, we isolated a novel human cDNA, designated Hu-ERK-3, from a fetal skeletal muscle library. Analysis of the complete 3,920-bp nucleotide sequence revealed that this clone encodes a predicted protein of 721 amino acids. In vitro transcription-translation generates a 97-kDa protein referred to as p97MAPK. Of all of the sequences compared, p97MAPK is the most homologous to rat ERK-3. Interestingly, although p97MAPK is highly (98%) homologous to ERK-3 at the amino acid level within the N-terminal two-thirds of the coding region, it diverges at the carboxyl terminus as a result of a unique extension of 178 amino acids. Although expression of p97MAPK was detected in all of the tissues tested by Northern (RNA) analysis, the most abundant expression was seen in skeletal muscle. An antibody raised against the unique C terminus recognized a 97-kDa protein in human cells. By using this antibody in an immune complex protein kinase assay, we have shown that treatment of human fibroblasts with serum or phorbol esters activates a myelin basic protein and histone H1 kinase activity in immunoprecipitates. p97MAPK appears to be the human homolog of rat ERK-3, and a member of this family is an active protein kinase.
47
Park, Soyoung, Ali H. Abdel Sater, Johannes F. Fahrmann, Ehsan Irajizad, Yining Cai, Hiroyuki Katayama, Jody Vykoukal, et al. "Novel UHRF1-MYC Axis in Acute Lymphoblastic Leukemia." Cancers 14, no. 17 (August 31, 2022): 4262. http://dx.doi.org/10.3390/cancers14174262.
Full textAbstract:
Ubiquitin-like, containing PHD and RING finger domain, (UHRF) family members are overexpressed putative oncogenes in several cancer types. We evaluated the protein abundance of UHRF family members in acute leukemia. A marked overexpression of UHRF1 protein was observed in ALL compared with AML. An analysis of human leukemia transcriptomic datasets revealed concordant overexpression of UHRF1 in B-Cell and T-Cell ALL compared with CLL, AML, and CML. In-vitro studies demonstrated reduced cell viability with siRNA-mediated knockdown of UHRF1 in both B-ALL and T-ALL, associated with reduced c-Myc protein expression. Mechanistic studies indicated that UHRF1 directly interacts with c-Myc, enabling ALL expansion via the CDK4/6-phosphoRb axis. Our findings highlight a previously unknown role of UHRF1 in regulating c-Myc protein expression and implicate UHRF1 as a potential therapeutic target in ALL.
48
Hu, Bo, Kien Trinh, William F. Figueira, and Paul A. Price. "Isolation and Sequence of a Novel Human Chondrocyte Protein Related to Mammalian Members of the Chitinase Protein Family." Journal of Biological Chemistry 271, no. 32 (August 9, 1996): 19415–20. http://dx.doi.org/10.1074/jbc.271.32.19415.
Full text
49
Crompton, M. R., R. J. Owens, N. F. Totty, S. E. Moss, M. D. Waterfield, and M. J. Crumpton. "Primary structure of the human, membrane-associated Ca2+-binding protein p68 a novel member of a protein family." EMBO Journal 7, no. 1 (January 1988): 21–27. http://dx.doi.org/10.1002/j.1460-2075.1988.tb02779.x.
Full text
50
Chen, Na, Taobo Hu, Yuanyuan Gui, Jieying Gao, Zhihong Li, and Shi Huang. "Transcriptional regulation of Bcl-2 gene by the PR/SET domain family member PRDM10." PeerJ 7 (May 15, 2019): e6941. http://dx.doi.org/10.7717/peerj.6941.
Full textAbstract:
Bcl-2 (B-cell lymphoma 2) protein is localized in the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. PRDM10 is a member of the PR/SET family of epigenetic regulators and may play a role in development and cell differentiation. Here we show that human PRDM10 contributes to the transcriptional regulation of human Bcl-2 gene. We found that PRDM10-depletion in human cells reduced the expression of Bcl-2 protein and over-expression of PRDM10 promoted Bcl-2 protein expression. Furthermore, luciferase reporter activity of Bcl-2 gene P1 promoter was significantly increased in cells co-transfected with PRDM10, and PRDM10 was able to bind to the Bcl-2 P1 promoterin vivo. Using The Cancer Genome Atlas (TCGA) data set, we found weak positive correlation between PRDM10 and Bcl-2 in several cancer types including cancers of the breast, colon, and lung tissues. These data identify a novel function for PRDM10 protein and provide insights on the transcriptional control of Bcl-2 expression.