Journal articles: 'Sfp1'

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Bielaszewska, Martina, Rita Prager, Liz Vandivinit, Anne Mï¿½sken, Alexander Mellmann, Nicholas J. Holt, Phillip I. Tarr, Helge Karch, and Wenlan Zhang. "Detection and Characterization of the Fimbrial sfp Cluster in Enterohemorrhagic Escherichia coli O165:H25/NM Isolates from Humans and Cattle." Applied and Environmental Microbiology 75, no. 1 (October 31, 2008): 64–71. http://dx.doi.org/10.1128/aem.01815-08.

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ABSTRACT The sfp cluster, encoding Sfp fimbriae and located in the large plasmid of sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157 (pSFO157), has been considered a unique characteristic of this organism. We discovered and then characterized the sfp cluster in EHEC O165:H25/NM (nonmotile) isolates of human and bovine origin. All seven strains investigated harbored a complete sfp cluster (carrying sfpA, sfpH, sfpC, sfpD, sfpJ, sfpF, and sfpG) of 6,838 bp with >99% nucleotide sequence homology to the sfp cluster of SF EHEC O157:NM. The sfp cluster in EHEC O165:H25/NM strains was located in an ∼80-kb (six strains) or ∼120-kb (one strain) plasmid which differed in structure, virulence genes, and sfp flanks from pSFO157. All O165:H25/NM strains belonged to the same multilocus sequence type (ST119) and were only distantly phylogenetically related to SF EHEC O157:NM (ST11). The highly conserved sfp cluster in different clonal backgrounds suggests that this segment was acquired independently by EHEC O165:H25 and SF EHEC O157:NM. Its presence in an additional EHEC serotype extends the diagnostic utility of PCR targeting sfpA as an easy and efficient approach to seek EHEC in patients' stools. The reasons for the convergence of pathogenic EHEC strains on a suite of virulence loci remain unknown.

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Xu, Zhiheng, and David Norris. "The SFP1 Gene Product of Saccharomyces cerevisiae Regulates G2/M Transitions During the Mitotic Cell Cycle and DNA-Damage Response." Genetics 150, no. 4 (December 1, 1998): 1419–28. http://dx.doi.org/10.1093/genetics/150.4.1419.

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Abstract In eukaryotic cells, checkpoint pathways arrest cell-cycle progression if a particular event has failed to complete appropriately or if an important intracellular structure is defective or damaged. Saccharomyces cerevisiae strains that lack the SFP1 gene fail to arrest at the G2 DNA-damage checkpoint in response to genomic injury, but maintain their ability to arrest at the replication and spindle-assembly checkpoints. sfp1Δ mutants are characterized by a premature entrance into mitosis during a normal (undamaged) cell cycle, while strains that overexpress Sfp1p exhibit delays in G2. Sfp1p therefore acts as a repressor of the G2/M transition, both in the normal cell cycle and in the G2 checkpoint pathway. Sfp1 is a nuclear protein with two Cys2His2 zinc-finger domains commonly found in transcription factors. We propose that Sfp1p regulates the expression of gene products involved in the G2/M transition during the mitotic cell cycle and the DNA-damage response. In support of this model, overexpression of Sfp1p induces the expression of the PDS1 gene, which is known to encode a protein that regulates the G2 checkpoint.

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Brunder, Werner, A. Salam Khan, Jörg Hacker, and Helge Karch. "Novel Type of Fimbriae Encoded by the Large Plasmid of Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:H−." Infection and Immunity 69, no. 7 (July 1, 2001): 4447–57. http://dx.doi.org/10.1128/iai.69.7.4447-4457.2001.

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ABSTRACT Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H− have emerged as important causes of diarrheal diseases and the hemolytic-uremic syndrome in Germany. In this study, we characterized a 32-kb fragment of the plasmid of SF EHEC O157:H−, pSFO157, which differs markedly from plasmid pO157 of classical non-sorbitol-fermenting EHEC O157:H7. We found a cluster of six genes, termed sfpA,sfpH, sfpC, sfpD,sfpJ, and sfpG, which mediate mannose-resistant hemagglutination and the expression of fimbriae.sfp genes are similar to the pap genes, encoding P-fimbriae of uropathogenic E. coli, but thesfp cluster lacks homologues of genes encoding subunits of a tip fibrillum as well as regulatory genes. The major pilin, SfpA, despite its similarity to PapA, does not cluster together with known PapA alleles in a phylogenetic tree but is structurally related to the PmpA pilin of Proteus mirabilis. The putative adhesin gene sfpG, responsible for the hemagglutination phenotype, shows significant homology neither to papGnor to other known sequences. Sfp fimbriae are 3 to 5 nm in diameter, in contrast to P-fimbriae, which are 7 nm in diameter. PCR analyses showed that the sfp gene cluster is a characteristic of SF EHEC O157:H− strains and is not present in other EHEC isolates, diarrheagenic E. coli, or otherEnterobacteriaceae. The sfp gene cluster is flanked by two blocks of insertion sequences and an origin of plasmid replication, indicating that horizontal gene transfer may have contributed to the presence of Sfp fimbriae in SF EHEC O157:H−.

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Meng, Kun, Jiang Li, Yanan Cao, Pengjun Shi, Bo Wu, Xiaoyu Han, Yingguo Bai, Ningfeng Wu, and Bin Yao. "Gene cloning and heterologous expression of a serine protease fromStreptomyces fradiaevar.k11." Canadian Journal of Microbiology 53, no. 2 (February 2007): 186–95. http://dx.doi.org/10.1139/w06-122.

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The gene sfp1, which encodes a predicted serine proteinase designated SFP1, was isolated by the screening of a gene library of the feather-degrading strain Streptomyces fradiae var.k11. The open reading frame of sfp1 encodes a protein of 454 amino acids with a calculated molecular mass of 46.19 kDa. Sequence analysis reveals that SFP1 possesses a typical pre-pro-mature organization that consists of a signal sequence, an N-terminal propeptide region, and a mature proteinase domain. The pre-enzyme of SFP1 was expressed in Escherichia coli and consequently purified. The 25.6 kDa fraction with protease activity separated by gel filtration chromatography indicated that the mature enzyme of SFP1 was formed by autolysis of the propeptide after its expression. The purified SFP1 is active under a broad range of pH and temperature. SFP1 has pH and temperature optima of pH 8.5 and 65 °C for its caseinolytic activity and pH 9 and 62 °C for its keratinolytic activity. SFP1 was sharply inhibited by the serine proteinase inhibitor phenylmethyl sulfonyl fluoride and exhibited a good stability to solvents, detergents, and salts. Comparison of the protease activity of SFP1 with other commercial proteases indicates that SFP1 has a considerable caseinolytic and keratinolytic activity as does proteinase K.

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Fingerman, Ian, Vijayalakshmi Nagaraj, David Norris, and Andrew K. Vershon. "Sfp1 Plays a Key Role in Yeast Ribosome Biogenesis." Eukaryotic Cell 2, no. 5 (October 2003): 1061–68. http://dx.doi.org/10.1128/ec.2.5.1061-1068.2003.

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ABSTRACT Sfp1, an unusual zinc finger protein, was previously identified as a gene that, when overexpressed, imparted a nuclear localization defect. sfp1 cells have a reduced size and a slow growth phenotype. In this study we show that SFP1 plays a role in ribosome biogenesis. An sfp1 strain is hypersensitive to drugs that inhibit translational machinery. sfp1 strains also have defects in global translation as well as defects in rRNA processing and 60S ribosomal subunit export. Microarray analysis has previously shown that ectopically expressed SFP1 induces the transcription of a large subset of genes involved in ribosome biogenesis. Many of these induced genes contain conserved promoter elements (RRPE and PAC). Our results show that activation of transcription from a reporter construct containing two RRPE sites flanking a single PAC element is SFP1 dependent. However, we have been unable to detect direct binding of the protein to these elements. This suggests that regulation of genes containing RRPEs is dependent upon Sfp1 but that Sfp1 may not directly bind to these conserved promoter elements; rather, activation may occur through an indirect mechanism.

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Lopez, Antonio Diaz, Krisztina Tar, Undine Krügel, Thomas Dange, Ignacio Guerrero Ros, and Marion Schmidt*. "Proteasomal degradation of Sfp1 contributes to the repression of ribosome biogenesis during starvation and is mediated by the proteasome activator Blm10." Molecular Biology of the Cell 22, no. 5 (March 2011): 528–40. http://dx.doi.org/10.1091/mbc.e10-04-0352.

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The regulation of ribosomal protein (RP) gene transcription is tightly linked to the nutrient status of the cell and is under the control of metabolic signaling pathways. In Saccharomyces cerevisiae several transcriptional activators mediate efficient RP gene transcription during logarithmic growth and dissociate from RP gene promoters upon nutrient limitation. Repression of RP gene transcription appears to be regulated predominantly by posttranslational modification and cellular localization of transcriptional activators. We report here that one of these factors, Sfp1, is degraded by the proteasome and that the proteasome activator Blm10 is required for regulated Sfp1 degradation. Loss of Blm10 results in the stabilization and increased nuclear abundance of Sfp1 during nutrient limitation, increased transcription of RP genes, increased levels of RPs, and decreased rapamycin-induced repression of RP genes. Thus we conclude that proteasomal degradation of Sfp1 is mediated by Blm10 and contributes to the repression of ribosome biogenesis under nutrient depletion.

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Chang, Che-Kang, Min-Chi Yang, Hsueh-Fen Chen, Yi-Ling Liao, and Chung-Yu Lan. "The Role of Sfp1 in Candida albicans Cell Wall Maintenance." Journal of Fungi 8, no. 11 (November 13, 2022): 1196. http://dx.doi.org/10.3390/jof8111196.

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The cell wall is the first interface for Candida albicans interaction with the surrounding environment and the host cells. Therefore, maintenance of cell wall integrity (CWI) is crucial for C. albicans survival and host-pathogen interaction. In response to environmental stresses, C. albicans undergoes cell wall remodeling controlled by multiple signaling pathways and transcription regulators. Here, we explored the role of the transcription factor Sfp1 in CWI. A deletion of the SFP1 gene not only caused changes in cell wall properties, cell wall composition and structure but also modulated expression of cell wall biosynthesis and remodeling genes. In addition, Cas5 is a known transcription regulator for C. albicans CWI and cell wall stress response. Interestingly, our results indicated that Sfp1 negatively controls the CAS5 gene expression by binding to its promoter element. Together, this study provides new insights into the regulation of C. albicans CWI and stress response.

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Lee, Shao-Yu, Hsueh-Fen Chen, Ying-Chieh Yeh, Yao-Peng Xue, and Chung-Yu Lan. "The Transcription Factor Sfp1 Regulates the Oxidative Stress Response in Candida albicans." Microorganisms 7, no. 5 (May 14, 2019): 131. http://dx.doi.org/10.3390/microorganisms7050131.

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Candida albicans is a commensal that inhabits the skin and mucous membranes of humans. Because of the increasing immunocompromised population and the limited classes of antifungal drugs available, C. albicans has emerged as an important opportunistic pathogen with high mortality rates. During infection and therapy, C. albicans frequently encounters immune cells and antifungal drugs, many of which exert their antimicrobial activity by inducing the production of reactive oxygen species (ROS). Therefore, antioxidative capacity is important for the survival and pathogenesis of C. albicans. In this study, we characterized the roles of the zinc finger transcription factor Sfp1 in the oxidative stress response against C. albicans. A sfp1-deleted mutant was more resistant to oxidants and macrophage killing than wild-type C. albicans and processed an active oxidative stress response with the phosphorylation of the mitogen-activated protein kinase (MAPK) Hog1 and high CAP1 expression. Moreover, the sfp1-deleted mutant exhibited high expression levels of antioxidant genes in response to oxidative stress, resulting in a higher total antioxidant capacity, glutathione content, and glutathione peroxidase and superoxide dismutase enzyme activity than the wild-type C. albicans. Finally, the sfp1-deleted mutant was resistant to macrophage killing and ROS-generating antifungal drugs. Together, our findings provide a new understanding of the complex regulatory machinery in the C. albicans oxidative stress response.

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Hosiner, Dagmar, Harri Lempiäinen, Wolfgang Reiter, Joerg Urban, Robbie Loewith, Gustav Ammerer, Rudolf Schweyen, David Shore, and Christoph Schüller. "Arsenic Toxicity to Saccharomyces cerevisiae Is a Consequence of Inhibition of the TORC1 Kinase Combined with a Chronic Stress Response." Molecular Biology of the Cell 20, no. 3 (February 2009): 1048–57. http://dx.doi.org/10.1091/mbc.e08-04-0438.

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The conserved Target Of Rapamycin (TOR) growth control signaling pathway is a major regulator of genes required for protein synthesis. The ubiquitous toxic metalloid arsenic, as well as mercury and nickel, are shown here to efficiently inhibit the rapamycin-sensitive TORC1 (TOR complex 1) protein kinase. This rapid inhibition of the TORC1 kinase is demonstrated in vivo by the dephosphorylation and inactivation of its downstream effector, the yeast S6 kinase homolog Sch9. Arsenic, mercury, and nickel cause reduction of transcription of ribosome biogenesis genes, which are under the control of Sfp1, a TORC1-regulated transcriptional activator. We report that arsenic stress deactivates Sfp1 as it becomes dephosphorylated, dissociates from chromatin, and exits the nucleus. Curiously, whereas loss of SFP1 function leads to increased arsenic resistance, absence of TOR1 or SCH9 has the opposite effect suggesting that TORC1 has a role beyond down-regulation of Sfp1. Indeed, we show that arsenic activates the transcription factors Msn2 and Msn4 both of which are targets of TORC1 and protein kinase A (PKA). In contrast to TORC1, PKA activity is not repressed during acute arsenic stress. A normal level of PKA activity might serve to dampen the stress response since hyperactive Msn2 will decrease arsenic tolerance. Thus arsenic toxicity in yeast might be determined by the balance between chronic activation of general stress factors in combination with lowered TORC1 kinase activity.

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Hsu, Chun-Min, Yi-Ling Liao, Che-Kang Chang, and Chung-Yu Lan. "Candida albicans Sfp1 Is Involved in the Cell Wall and Endoplasmic Reticulum Stress Responses Induced by Human Antimicrobial Peptide LL-37." International Journal of Molecular Sciences 22, no. 19 (September 30, 2021): 10633. http://dx.doi.org/10.3390/ijms221910633.

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Candida albicans is a commensal fungus of humans but can cause infections, particularly in immunocompromised individuals, ranging from superficial to life-threatening systemic infections. The cell wall is the outermost layer of C. albicans that interacts with the host environment. Moreover, antimicrobial peptides (AMPs) are important components in innate immunity and play crucial roles in host defense. Our previous studies showed that the human AMP LL-37 binds to the cell wall of C. albicans, alters the cell wall integrity (CWI) and affects cell adhesion of this pathogen. In this study, we aimed to further investigate the molecular mechanisms underlying the C. albicans response to LL-37. We found that LL-37 causes cell wall stress, activates unfolded protein response (UPR) signaling related to the endoplasmic reticulum (ER), induces ER-derived reactive oxygen species and affects protein secretion. Interestingly, the deletion of the SFP1 gene encoding a transcription factor reduced C. albicans susceptibility to LL-37, which is cell wall-associated. Moreover, in the presence of LL-37, deletion of SFP1 attenuated the UPR pathway, upregulated oxidative stress responsive (OSR) genes and affected bovine serum albumin (BSA) degradation by secreted proteases. Therefore, these findings suggested that Sfp1 positively regulates cell wall integrity and ER homeostasis upon treatment with LL-37 and shed light on pathogen-host interactions.

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Zencir, Sevil, Daniel Dilg, Maria Paula Rueda, David Shore, and Benjamin Albert. "Mechanisms coordinating ribosomal protein gene transcription in response to stress." Nucleic Acids Research 48, no. 20 (October 21, 2020): 11408–20. http://dx.doi.org/10.1093/nar/gkaa852.

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Abstract While expression of ribosomal protein genes (RPGs) in the budding yeast has been extensively studied, a longstanding enigma persists regarding their co-regulation under fluctuating growth conditions. Most RPG promoters display one of two distinct arrangements of a core set of transcription factors (TFs) and are further differentiated by the presence or absence of the HMGB protein Hmo1. However, a third group of promoters appears not to be bound by any of these proteins, raising the question of how the whole suite of genes is co-regulated. We demonstrate here that all RPGs are regulated by two distinct, but complementary mechanisms driven by the TFs Ifh1 and Sfp1, both of which are required for maximal expression in optimal conditions and coordinated downregulation upon stress. At the majority of RPG promoters, Ifh1-dependent regulation predominates, whereas Sfp1 plays the major role at all other genes. We also uncovered an unexpected protein homeostasis-dependent binding property of Hmo1 at RPG promoters. Finally, we show that the Ifh1 paralog Crf1, previously described as a transcriptional repressor, can act as a constitutive RPG activator. Our study provides a more complete picture of RPG regulation and may serve as a paradigm for unravelling RPG regulation in multicellular eukaryotes.

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Lengerer, Birgit, Morgane Algrain, Mathilde Lefevre, Jérôme Delroisse, Elise Hennebert, and Patrick Flammang. "Interspecies comparison of sea star adhesive proteins." Philosophical Transactions of the Royal Society B: Biological Sciences 374, no. 1784 (September 9, 2019): 20190195. http://dx.doi.org/10.1098/rstb.2019.0195.

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Sea stars use adhesive secretions to attach their numerous tube feet strongly and temporarily to diverse surfaces. After detachment of the tube feet, the adhesive material stays bound to the substrate as so-called ‘footprints’. In the common sea star species Asterias rubens , the adhesive material has been studied extensively and the first sea star footprint protein (Sfp1) has been characterized. We identified Sfp1-like sequences in 17 additional sea star species, representing different taxa and tube foot morphologies, and analysed the evolutionary conservation of this protein. In A. rubens , we confirmed the expression of 34 footprint proteins in the tube foot adhesive epidermis, with 22 being exclusively expressed in secretory cells of the adhesive epidermis and 12 showing an additional expression in the stem epidermis. The sequences were used for BLAST searches in seven asteroid transcriptomes providing a first insight in the conservation of footprint proteins among sea stars. Our results highlighted a high conservation of the large proteins making up the structural core of the footprints, whereas smaller, potential surface-binding proteins might be more variable among sea star species. This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.

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Coleman, Chasity B., Patricia L. Allen, Mark Rupert, Carla Goulart, Alexander Hoehn, Louis S. Stodieck, and Timothy G. Hammond. "Novel Sfp1 Transcriptional Regulation ofSaccharomyces cerevisiaeGene Expression Changes During Spaceflight." Astrobiology 8, no. 6 (December 2008): 1071–78. http://dx.doi.org/10.1089/ast.2007.0211.

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Shore, David, Sevil Zencir, and Benjamin Albert. "Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals." Biochemical Society Transactions 49, no. 4 (July 9, 2021): 1589–99. http://dx.doi.org/10.1042/bst20201136.

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Ribosome biogenesis requires prodigious transcriptional output in rapidly growing yeast cells and is highly regulated in response to both growth and stress signals. This minireview focuses on recent developments in our understanding of this regulatory process, with an emphasis on the 138 ribosomal protein genes (RPGs) themselves and a group of >200 ribosome biogenesis (RiBi) genes whose products contribute to assembly but are not part of the ribosome. Expression of most RPGs depends upon Rap1, a pioneer transcription factor (TF) required for the binding of a pair of RPG-specific TFs called Fhl1 and Ifh1. RPG expression is correlated with Ifh1 promoter binding, whereas Rap1 and Fhl1 remain promoter-associated upon stress-induced down regulation. A TF called Sfp1 has also been implicated in RPG regulation, though recent work reveals that its primary function is in activation of RiBi and other growth-related genes. Sfp1 plays an important regulatory role at a small number of RPGs where Rap1–Fhl1–Ifh1 action is subsidiary or non-existent. In addition, nearly half of all RPGs are bound by Hmo1, which either stabilizes or re-configures Fhl1–Ifh1 binding. Recent studies identified the proline rotamase Fpr1, known primarily for its role in rapamycin-mediated inhibition of the TORC1 kinase, as an additional TF at RPG promoters. Fpr1 also affects Fhl1–Ifh1 binding, either independently or in cooperation with Hmo1. Finally, a major recent development was the discovery of a protein homeostasis mechanism driven by unassembled ribosomal proteins, referred to as the Ribosome Assembly Stress Response (RASTR), that controls RPG transcription through the reversible condensation of Ifh1.

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Chen, Hsueh-Fen, and Chung-Yu Lan. "Role of SFP1 in the Regulation of Candida albicans Biofilm Formation." PLOS ONE 10, no. 6 (June 18, 2015): e0129903. http://dx.doi.org/10.1371/journal.pone.0129903.

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Cipollina, Chiara, Joost van den Brink, Pascale Daran-Lapujade, Jack T. Pronk, Danilo Porro, and Johannes H. de Winde. "Saccharomyces cerevisiae SFP1: at the crossroads of central metabolism and ribosome biogenesis." Microbiology 154, no. 6 (June 1, 2008): 1686–99. http://dx.doi.org/10.1099/mic.0.2008/017392-0.

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Lempiäinen, Harri, Aino Uotila, Jörg Urban, Ilse Dohnal, Gustav Ammerer, Robbie Loewith, and David Shore. "Sfp1 Interaction with TORC1 and Mrs6 Reveals Feedback Regulation on TOR Signaling." Molecular Cell 33, no. 6 (March 2009): 704–16. http://dx.doi.org/10.1016/j.molcel.2009.01.034.

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Cipollina, Chiara, Lilia Alberghina, Danilo Porro, and Marina Vai. "SFP1 is involved in cell size modulation in respiro-fermentative growth conditions." Yeast 22, no. 5 (2005): 385–99. http://dx.doi.org/10.1002/yea.1218.

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Marion, R. M., A. Regev, E. Segal, Y. Barash, D. Koller, N. Friedman, and E. K. O'Shea. "Sfp1 is a stress- and nutrient-sensitive regulator of ribosomal protein gene expression." Proceedings of the National Academy of Sciences 101, no. 40 (September 7, 2004): 14315–22. http://dx.doi.org/10.1073/pnas.0405353101.

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Albert, Benjamin, Susanna Tomassetti, Yvonne Gloor, Daniel Dilg, Stefano Mattarocci, Slawomir Kubik, Lukas Hafner, and David Shore. "Sfp1 regulates transcriptional networks driving cell growth and division through multiple promoter-binding modes." Genes & Development 33, no. 5-6 (February 25, 2019): 288–93. http://dx.doi.org/10.1101/gad.322040.118.

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Drozdova, P. B., E. A. Radchenko, T. M. Rogoza, M. A. Khokhrina, and L. N. Mironova. "The SFP1 controls translation termination in Saccharomyces cerevisiae via regulation of Sup35p (eRF3) level." Molecular Biology 47, no. 2 (March 2013): 242–47. http://dx.doi.org/10.1134/s0026893313010044.

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Mathew, Veena, Annie S. Tam, Karissa L. Milbury, Analise K. Hofmann, Christopher S. Hughes, Gregg B. Morin, Christopher J. R. Loewen, and Peter C. Stirling. "Selective aggregation of the splicing factor Hsh155 suppresses splicing upon genotoxic stress." Journal of Cell Biology 216, no. 12 (October 4, 2017): 4027–40. http://dx.doi.org/10.1083/jcb.201612018.

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Upon genotoxic stress, dynamic relocalization events control DNA repair as well as alterations of the transcriptome and proteome, enabling stress recovery. How these events may influence one another is only partly known. Beginning with a cytological screen of genome stability proteins, we find that the splicing factor Hsh155 disassembles from its partners and localizes to both intranuclear and cytoplasmic protein quality control (PQC) aggregates under alkylation stress. Aggregate sequestration of Hsh155 occurs at nuclear and then cytoplasmic sites in a manner that is regulated by molecular chaperones and requires TORC1 activity signaling through the Sfp1 transcription factor. This dynamic behavior is associated with intron retention in ribosomal protein gene transcripts, a decrease in splicing efficiency, and more rapid recovery from stress. Collectively, our analyses suggest a model in which some proteins evicted from chromatin and undergoing transcriptional remodeling during stress are targeted to PQC sites to influence gene expression changes and facilitate stress recovery.

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Li, Zhongming, and Kwang Sik Kim. "RELATe enables genome-scale engineering in fungal genomics." Science Advances 6, no. 38 (September 2020): eabb8783. http://dx.doi.org/10.1126/sciadv.abb8783.

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CRISPR-Cas9–based screening with single-guide RNA (sgRNA) libraries has emerged as a revolutionary tool for comprehensive analysis of genetic elements. However, genome-scale sgRNA libraries are currently available only in a few model organisms. The traditional approach is to synthesize thousands to tens of thousands of sgRNAs, which is laborious and expensive. We have developed a simple method, RELATe (restriction/ligation coupled with Agrobacterium-mediated transformation), to generate sgRNA libraries from 10 μg of genomic DNA, targeting over 98% of the protein-coding genes in the human fungal pathogen Cryptococcus neoformans. Functional screens identified 142 potential C. neoformans genes contributing to blood-brain barrier penetration. We selected two cryptococcal genes, SFP1 and WDR1, for a proof-of-concept demonstration that RELATe-identified genes are relevant to C. neoformans central nervous system infection. Our RELATe method can be used in many other fungal species and is powerful and cost-effective for genome-wide high-throughput screening for elucidating functional genomics.

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Saif, Saima, and Mohammad Saghir Khan. "Biosorbing Potentials of Pseudomonas aeruginosa SFP1 to Combat Cr(VI) Stress in Cicer Arietinum Seedlings." Journal of Energy and Environmental Sustainability 7 (January 31, 2019): 5–9. http://dx.doi.org/10.47469/jees.2019.v07.100069.

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Kastora, Stavroula L., Carmen Herrero‐de‐Dios, Gabriela M. Avelar, Carol A. Munro, and Alistair J. P. Brown. "Sfp1 and Rtg3 reciprocally modulate carbon source‐conditional stress adaptation in the pathogenic yeastCandida albicans." Molecular Microbiology 105, no. 4 (June 19, 2017): 620–36. http://dx.doi.org/10.1111/mmi.13722.

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Matveenko, Andrew G., Polina B. Drozdova, Mikhail V. Belousov, Svetlana E. Moskalenko, Stanislav A. Bondarev, Yury A. Barbitoff, Anton A. Nizhnikov, and Galina A. Zhouravleva. "SFP1-mediated prion-dependent lethality is caused by increased Sup35 aggregation and alleviated by Sis1." Genes to Cells 21, no. 12 (October 12, 2016): 1290–308. http://dx.doi.org/10.1111/gtc.12444.

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Khan, Shagufta A., Amol R. Suryawanshi, Sandeep A. Ranpura, Sudhir V. Jadhav, and Vrinda V. Khole. "Identification of novel immunodominant epididymal sperm proteins using combinatorial approach." REPRODUCTION 138, no. 1 (July 2009): 81–93. http://dx.doi.org/10.1530/rep-09-0052.

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Functionally immature spermatozoa leave the testis mature during epididymal transit. This process of maturation involves either addition of new proteins or modification of existing proteins onto the sperm domains that are responsible for domain-specific functions. Epididymal proteins are preferred targets for immunocontraception. In an attempt to identify epididymis-specific sperm proteins, we used a novel combinatorial approach comprising subtractive immunization (SI) followed by proteomics. Following SI, sera of mice were used for immunoproteomics, which led to the identification of 30 proteins, of which four proteins namely sperm head protein 1, sperm flagella protein 2 (SFP2), SFP3, and SFP4 are being reported for the first time on sperm. Another group of four proteins namely collagen α-2 (I) chain precursor, homeodomain-interacting protein kinase 1, GTP-binding protein Rab1, and ubiquinol cytochrome c reductase core protein II although reported earlier in testis are being reported for the first time in epididymal sperm. Furthermore, seven out of these eight novel proteins could be validated using peptide ELISA. These data are a useful repository, which could be exploited to develop targets for post-testicular immunocontraception or biomarkers for infertility diagnosis and management.

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Teixeira, Vitor, Telma S. Martins, William A. Prinz, and Vítor Costa. "Target of Rapamycin Complex 1 (TORC1), Protein Kinase A (PKA) and Cytosolic pH Regulate a Transcriptional Circuit for Lipid Droplet Formation." International Journal of Molecular Sciences 22, no. 16 (August 20, 2021): 9017. http://dx.doi.org/10.3390/ijms22169017.

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Lipid droplets (LDs) are ubiquitous organelles that fulfill essential roles in response to metabolic cues. The identification of several neutral lipid synthesizing and regulatory protein complexes have propelled significant advance on the mechanisms of LD biogenesis in the endoplasmic reticulum (ER). However, our understanding of signaling networks, especially transcriptional mechanisms, regulating membrane biogenesis is very limited. Here, we show that the nutrient-sensing Target of Rapamycin Complex 1 (TORC1) regulates LD formation at a transcriptional level, by targeting DGA1 expression, in a Sit4-, Mks1-, and Sfp1-dependent manner. We show that cytosolic pH (pHc), co-regulated by the plasma membrane H+-ATPase Pma1 and the vacuolar ATPase (V-ATPase), acts as a second messenger, upstream of protein kinase A (PKA), to adjust the localization and activity of the major transcription factor repressor Opi1, which in turn controls the metabolic switch between phospholipid metabolism and lipid storage. Together, this work delineates hitherto unknown molecular mechanisms that couple nutrient availability and pHc to LD formation through a transcriptional circuit regulated by major signaling transduction pathways.

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Radchenko, Elina, Tatyana Rogoza, Maria Khokhrina, Polina Drozdova, and Ludmila Mironova. "SUP35 expression is enhanced in yeast containing [ISP+], a prion form of the transcriptional regulator Sfp1." Prion 5, no. 4 (October 2011): 317–22. http://dx.doi.org/10.4161/pri.18426.

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Radchenko, Elina, Tatyana Rogoza, Maria Khokhrina, Polina Drozdova, and Ludmila Mironova. "SUP35 expression is enhanced in yeast containing [ISP+], a prion form of the transcriptional regulator Sfp1." Prion 5, no. 4 (October 1, 2011): 317–22. http://dx.doi.org/10.4161/pri.5.4.18426.

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Cipollina, Chiara, Joost van den Brink, Pascale Daran-Lapujade, Jack T. Pronk, Marina Vai, and Johannes H. de Winde. "Revisiting the role of yeast Sfp1 in ribosome biogenesis and cell size control: a chemostat study." Microbiology 154, no. 1 (January 1, 2008): 337–46. http://dx.doi.org/10.1099/mic.0.2007/011767-0.

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Granados, Alejandro A., Julian M. J. Pietsch, Sarah A. Cepeda-Humerez, Iseabail L. Farquhar, Gašper Tkačik, and Peter S. Swain. "Distributed and dynamic intracellular organization of extracellular information." Proceedings of the National Academy of Sciences 115, no. 23 (May 21, 2018): 6088–93. http://dx.doi.org/10.1073/pnas.1716659115.

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Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.

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Rogoza, T., A. Goginashvili, S. Rodionova, M. Ivanov, O. Viktorovskaya, A. Rubel, K. Volkov, and L. Mironova. "Non-Mendelian determinant [ISP+] in yeast is a nuclear-residing prion form of the global transcriptional regulator Sfp1." Proceedings of the National Academy of Sciences 107, no. 23 (May 24, 2010): 10573–77. http://dx.doi.org/10.1073/pnas.1005949107.

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Padilla, C. A., J. A. Bárcena, M. J. López-Grueso, and R. Requejo-Aguilar. "The regulation of TORC1 pathway by the yeast chaperones Hsp31 is mediated by SFP1 and affects proteasomal activity." Biochimica et Biophysica Acta (BBA) - General Subjects 1863, no. 3 (March 2019): 534–46. http://dx.doi.org/10.1016/j.bbagen.2018.12.011.

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Jiang, Yuwei, Matthew D. Berg, Julie Genereaux, Khadija Ahmed, Martin L. Duennwald, Christopher J. Brandl, and Patrick Lajoie. "Sfp1 links TORC1 and cell growth regulation to the yeast SAGA‐complex component Tra1 in response to polyQ proteotoxicity." Traffic 20, no. 4 (March 15, 2019): 267–83. http://dx.doi.org/10.1111/tra.12637.

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Drozdova, Polina, Tatyana Rogoza, Elina Radchenko, Polina Lipaeva, and Ludmila Mironova. "Transcriptional response to the [ISP+] prion ofSaccharomyces cerevisiaediffers from that induced by the deletion of its structural gene,SFP1." FEMS Yeast Research 14, no. 8 (October 2, 2014): 1160–70. http://dx.doi.org/10.1111/1567-1364.12211.

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Busti, Stefano, Laura Gotti, Chiara Balestrieri, Lorenzo Querin, Guido Drovandi, Giovanni Felici, Gabriella Mavelli, Paola Bertolazzi, Lilia Alberghina, and Marco Vanoni. "Overexpression of Far1, a cyclin-dependent kinase inhibitor, induces a large transcriptional reprogramming in which RNA synthesis senses Far1 in a Sfp1-mediated way." Biotechnology Advances 30, no. 1 (January 2012): 185–201. http://dx.doi.org/10.1016/j.biotechadv.2011.09.007.

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Sharma, Kartik, Krisana Nilsuwan, Lukai Ma, and Soottawat Benjakul. "Effect of Liposomal Encapsulation and Ultrasonication on Debittering of Protein Hydrolysate and Plastein from Salmon Frame." Foods 12, no. 4 (February 9, 2023): 761. http://dx.doi.org/10.3390/foods12040761.

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The impacts of liposomal encapsulation on the bitterness of salmon frame protein hydrolysate (SFPH) and salmon frame protein plastein (SFPP) with the aid of ultrasound (20% amplitude, 750 W) for different time intervals (30, 60 and 120 s) were investigated. Liposomes loaded with 1% protein hydrolysate (L-PH1) and 1% plastein (L-PT1) showed the highest encapsulation efficiency and the least bitterness (p < 0.05). Ultrasonication for longer times reduced encapsulation efficiency (EE) and increased bitterness of both L-PH1 and L-PT1 along with a reduction in particle size. When comparing between L-PH1 and L-PT1, the latter showed less bitterness due to the lower bitterness in nature and higher entrapment of plastein in the liposomes. In vitro release studies also showed the delayed release of peptides from L-PT1 in comparison to the control plastein hydrolysate. Therefore, encapsulation of liposomes with 1% plastein could be an efficient delivery system for improving the sensory characteristics by lowering the bitterness of protein hydrolysates.

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Lee, I.-Ju, Ning Wang, Wen Hu, Kersey Schott, Jürg Bähler, Thomas H. Giddings, John R. Pringle, Li-Lin Du, and Jian-Qiu Wu. "Regulation of spindle pole body assembly and cytokinesis by the centrin-binding protein Sfi1 in fission yeast." Molecular Biology of the Cell 25, no. 18 (September 15, 2014): 2735–49. http://dx.doi.org/10.1091/mbc.e13-11-0699.

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Centrosomes play critical roles in the cell division cycle and ciliogenesis. Sfi1 is a centrin-binding protein conserved from yeast to humans. Budding yeast Sfi1 is essential for the initiation of spindle pole body (SPB; yeast centrosome) duplication. However, the recruitment and partitioning of Sfi1 to centrosomal structures have never been fully investigated in any organism, and the presumed importance of the conserved tryptophans in the internal repeats of Sfi1 remains untested. Here we report that in fission yeast, instead of doubling abruptly at the initiation of SPB duplication and remaining at a constant level thereafter, Sfi1 is gradually recruited to SPBs throughout the cell cycle. Like an sfi1Δ mutant, a Trp-to-Arg mutant (sfi1-M46) forms monopolar spindles and exhibits mitosis and cytokinesis defects. Sfi1-M46 protein associates preferentially with one of the two daughter SPBs during mitosis, resulting in a failure of new SPB assembly in the SPB receiving insufficient Sfi1. Although all five conserved tryptophans tested are involved in Sfi1 partitioning, the importance of the individual repeats in Sfi1 differs. In summary, our results reveal a link between the conserved tryptophans and Sfi1 partitioning and suggest a revision of the model for SPB assembly.

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Rüthnick, Diana, and Elmar Schiebel. "Duplication of the Yeast Spindle Pole Body Once per Cell Cycle." Molecular and Cellular Biology 36, no. 9 (March 7, 2016): 1324–31. http://dx.doi.org/10.1128/mcb.00048-16.

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The yeast spindle pole body (SPB) is the functional equivalent of the mammalian centrosome. Centrosomes and SPBs duplicate exactly once per cell cycle by mechanisms that use the mother structure as a platform for the assembly of the daughter. The conserved Sfi1 and centrin proteins are essential components of the SPB duplication process. Sfi1 is an elongated molecule that has, in its center, 20 to 23 binding sites for the Ca2+-binding protein centrin. In the yeastSaccharomyces cerevisiae, all Sfi1 N termini are in contact with the mother SPB whereas the free C termini are distal to it. During S phase and early mitosis, cyclin-dependent kinase 1 (Cdk1) phosphorylation of mainly serine residues in the Sfi1 C termini blocks the initiation of SPB duplication (“off” state). Upon anaphase onset, the phosphatase Cdc14 dephosphorylates Sfi1 (“on” state) to promote antiparallel and shifted incorporation of cytoplasmic Sfi1 molecules into the half-bridge layer, which thereby elongates into the bridge. The Sfi1 C termini of the two Sfi1 layers localize in the bridge center, whereas the N termini of the newly assembled Sfi1 molecules are distal to the mother SPB. These free Sfi1 N termini then assemble the new SPB in G1phase. Recruitment of Sfi1 molecules into the anaphase SPB and bridge formation were also observed inSchizosaccharomyces pombe, suggesting that the Sfi1 bridge cycle is conserved between the two organisms. Thus, restricting SPB duplication to one event per cell cycle requires only an oscillation between Cdk1 kinase and Cdc14 phosphatase activities. This clockwork regulates the “on”/“off” state of the Sfi1-centrin receiver.

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Huang, Jie, Mitchell Ringuet, Andrew E. Whitten, Sofia Caria, Yee Wa Lim, Rahul Badhan, Victor Anggono, and Mihwa Lee. "Structural basis of the zinc-induced cytoplasmic aggregation of the RNA-binding protein SFPQ." Nucleic Acids Research 48, no. 6 (February 8, 2020): 3356–65. http://dx.doi.org/10.1093/nar/gkaa076.

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Abstract SFPQ is a ubiquitous nuclear RNA-binding protein implicated in many aspects of RNA biogenesis. Importantly, nuclear depletion and cytoplasmic accumulation of SFPQ has been linked to neuropathological conditions such as Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). Here, we describe a molecular mechanism by which SFPQ is mislocalized to the cytoplasm. We report an unexpected discovery of the infinite polymerization of SFPQ that is induced by zinc binding to the protein. The crystal structure of human SFPQ in complex with zinc at 1.94 Å resolution reveals intermolecular interactions between SFPQ molecules that are mediated by zinc. As anticipated from the crystal structure, the application of zinc to primary cortical neurons induced the cytoplasmic accumulation and aggregation of SFPQ. Mutagenesis of the three zinc-coordinating histidine residues resulted in a significant reduction in the zinc-binding affinity of SFPQ in solution and the zinc-induced cytoplasmic aggregation of SFPQ in cultured neurons. Taken together, we propose that dysregulation of zinc availability and/or localization in neuronal cells may represent a mechanism for the imbalance in the nucleocytoplasmic distribution of SFPQ, which is an emerging hallmark of neurodegenerative diseases including AD and ALS.

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Seybold, Christian, Menattallah Elserafy, Diana Rüthnick, Musa Ozboyaci, Annett Neuner, Benjamin Flottmann, Mike Heilemann, Rebecca C. Wade, and Elmar Schiebel. "Kar1 binding to Sfi1 C-terminal regions anchors the SPB bridge to the nuclear envelope." Journal of Cell Biology 209, no. 6 (June 15, 2015): 843–61. http://dx.doi.org/10.1083/jcb.201412050.

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The yeast spindle pole body (SPB) is the functional equivalent of the mammalian centrosome. The half bridge is a SPB substructure on the nuclear envelope (NE), playing a key role in SPB duplication. Its cytoplasmic components are the membrane-anchored Kar1, the yeast centrin Cdc31, and the Cdc31-binding protein Sfi1. In G1, the half bridge expands into the bridge through Sfi1 C-terminal (Sfi1-CT) dimerization, the licensing step for SPB duplication. We exploited photo-activated localization microscopy (PALM) to show that Kar1 localizes in the bridge center. Binding assays revealed direct interaction between Kar1 and C-terminal Sfi1 fragments. kar1Δ cells whose viability was maintained by the dominant CDC31-16 showed an arched bridge, indicating Kar1’s function in tethering Sfi1 to the NE. Cdc31-16 enhanced Cdc31–Cdc31 interactions between Sfi1–Cdc31 layers, as suggested by binding free energy calculations. In our model, Kar1 binding is restricted to Sfi1-CT and Sfi1 C-terminal centrin-binding repeats, and centrin and Kar1 provide cross-links, while Sfi1-CT stabilizes the bridge and ensures timely SPB separation.

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Li, Yandong, Chang Su, Xuming Mao, Fang Cao, and Jiangye Chen. "Roles of Candida albicans Sfl1 in Hyphal Development." Eukaryotic Cell 6, no. 11 (August 22, 2007): 2112–21. http://dx.doi.org/10.1128/ec.00199-07.

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ABSTRACT The ability to switch between different morphological forms is an important feature of Candida albicans and is relevant to its pathogenesis. Many conserved positive and negative transcription factors are involved in morphogenetic regulation of the two dimorphic fungi Candida albicans and Saccharomyces cerevisiae. In S. cerevisiae, the transcriptional repressor Sfl1 and the activator Flo8 function antagonistically in invasive and filamentous growth. We have previously reported that Candida albicans Flo8 is a transcription factor essential for hyphal development and virulence in C. albicans. To determine whether a similar negative factor exists in C. albicans, we identified Candida albicans Sfl1 as a functional homolog of the S. cerevisiae sfl1 mutant. Sfl1 is a negative regulator of hyphal development in C. albicans. Deletion of C. albicans SFL1 enhanced filamentous growth and hypha-specific gene expression in several media and at several growth temperatures. Overexpression of the SFL1 led to a significant reduction of filament formation. Both deletion and overexpression of the SFL1 attenuated virulence of C. albicans in a mouse model. Deleting FLO8 in an sfl1/sfl1 mutant completely blocked hyphal development in various growth conditions examined, suggesting that C. albicans Sfl1 may act as a negative regulator of filamentous growth by antagonizing Flo8 functions. We suggest that, similar to the case for S. cerevisiae, a combination of dual control by activation and repression of Flo8 and Sfl1 may contribute to the fine regulatory network in C. albicans morphogenesis responding to different environmental cues.

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Zhao, Yujian, Shuo An, Hongchen Bi, Xiaoli Luo, Mingyang Wang, Aiming Pang, Erlie Jiang, Yigeng Cao, and Yujie Cui. "Evaluation of Platelet Parameters in Patients With Secondary Failure of Platelet Recovery and Cytomegalovirus Infection After Hematopoietic Stem Cell Transplantation." Clinical and Applied Thrombosis/Hemostasis 29 (January 2023): 107602962311577. http://dx.doi.org/10.1177/10760296231157741.

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Objective To investigate the clinical significance of changes in platelet parameters in patients with secondary failure of platelet recovery (SFPR) and cytomegalovirus (CMV) infection after hematopoietic stem cell transplantation (HSCT). Methods In this retrospective study, 79 patients who had undergone allogeneic HSCT (allo-HSCT), including 40 patients with SFPR and 39 patients without SFPR, were recruited. The evaluated parameters were platelet count (PLT), plateletcrit (PCT), platelet-large cell ratio (P-LCR), mean platelet volume (MPV), platelet distribution width (PDW), the incidence of CMV infection after allo-HSCT, and the correlation of SFPR and CMV infection in patients who had undergone allo-HSCT. The control group included 107 healthy donors. Results The SFPR group had significantly lower megakaryocyte counts, PLT, and PCT and significantly higher P-LCR, MPV, and PDW than the healthy donor and non-SFPR groups. The incidence of CMV infection was higher in SFPR patients than in non-SFPR patients. Among the patients with SFPR, P-LCR, MPV, and PDW were lower in those with CMV DNA >8000 copies/mL than in those with CMV DNA <8000 copies/mL ( P < .05 for all); the CMV viral load was slightly negatively correlated with MPV ( P = .0297) and P-LCR ( P = .0280). Conclusion We demonstrate for the first time that the level of platelet activation in SFPR patients, which was closely related to CMV infection, was higher than that in that in non-SFPR patients, and higher CMV load was associated with the inhibition of platelet activation.

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Brown, Lauren M., Hannah Huckstep, Jarrod Sandow, Ray C. Bartolo, Nadia Davidson, Breon Schmidt, Stefan Bjelosevic, et al. "Different Classes of ABL1 Fusions Activate Different Downstream Signalling Nodes." Blood 132, Supplement 1 (November 29, 2018): 2628. http://dx.doi.org/10.1182/blood-2018-99-117844.

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Abstract Background: Philadelphia-like acute lymphoblastic leukaemia (Ph-like ALL) is a high-risk subtype of ALL driven by a range of tyrosine kinase and cytokine receptor rearrangements. ABL1-class rearrangements (ABL1, ABL2, CSF1R and PDGFRB) account for 17% of Ph-like ALL cases in children, and are clinically important to identify as they can be therapeutically targeted with tyrosine kinase inhibitors (TKIs). While the p190 BCR-ABL1 fusion is well described, less is known about the function and downstream signalling by rare ABL1 fusions. We identified a rare ABL1 fusion, SFPQ-ABL1, in a paediatric B-ALL patient using RNA-sequencing. This fusion lacks the ABL1 Src-homology-3 (SH3) and part of the SH2 domain, which are retained in BCR-ABL1. Other ABL1 fusions, RCSD1-ABL1 and SNX2-ABL1, have a similar structure. In this work we have utilised phosphoproteomics and Stable Isotope Labelling by Amino Acids in Cell Culture (SILAC), as well as in vitro and in vivo models, to determine differential signalling pathways between SFPQ-ABL1 and BCR-ABL1. Methods: We cloned SFPQ-ABL1 from patient cDNA, and engineered SFPQ-ABL1 and BCR-ABL1 fusions to include or delete the SH2 and SH3 domains. We performed proliferation and viability assays to assess the ability of these fusions to transform Ba/F3 cells and test sensitivity to TKIs. We performed total phosphopeptide and phosphotyrosine enrichments and utilised mass spectrometry to identify the phosphoproteome activated by canonical SFPQ-ABL1 and BCR-ABL1. Over representation analysis was performed on phosphopeptides significantly differing between BCR-ABL and SFPQ-ABL (Log fold change cut-off > 2.5) using the Gene Ontology (GO) knowledge base under the biological process category. Furthermore, we compared the phosphoproteome of canonical SFPQ-ABL1 to SFPQ-ABL1 with the SH2 and SH3 domains reintroduced (SFPQ-ABL1+SH). We have also developed novel mouse models, using syngeneic transplantation, of SFPQ-ABL1 and SNX2-ABL1 driven leukaemia. Results: SFPQ-ABL1 expressing Ba/F3 cells are sensitive to cell death induced by TKIs that block ABL1. Interestingly, while SFPQ-ABL1 and BCR-ABL1 both effectively blocked apoptosis, SFPQ-ABL1 was less able to drive cytokine-independent proliferation. Phosphoproteomic analysis showed that BCR-ABL1 and SFPQ-ABL1 differentially activate downstream signalling pathways, including SH-binding proteins. Hierarchical clustering of phosphopeptides quantified from cells expressing canonical BCR-ABL1, SFPQ-ABL1, and SFPQ-ABL1+SH, demonstrated that BCR-ABL1 and SFPQ-ABL1+SH were more similar to each other than to SFPQ-ABL1. SFPQ-ABL1 expression resulted in phosphorylation of proteins involved in RNA processing, metabolism and splicing, suggesting that SFPQ region of SFPQ-ABL1 also contributes to signalling. Conclusions: In this study, we have utilised phosphoproteomics for the unbiased identification of signalling nodes that are required for the function of different classes of ABL fusions. We have developed novel in vitro and in vivo models to further understand how these fusions function to drive leukaemia. Our data also suggests that ABL1 fusion partners play a role beyond dimerization and transphosphorylation of the kinase domains in oncogenic signalling, but further study is needed to establish the contribution to leukaemogenesis. Establishing signalling pathways that are critical to the function of rare ABL1 fusions may inform clinical approaches to treating this disease. Disclosures No relevant conflicts of interest to declare.

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Xin, Ruijiao, Ling Zhu, Patrice A. Salomé, Estefania Mancini, Carine M. Marshall, Frank G. Harmon, Marcelo J. Yanovsky, Detlef Weigel, and Enamul Huq. "SPF45-related splicing factor for phytochrome signaling promotes photomorphogenesis by regulating pre-mRNA splicing in Arabidopsis." Proceedings of the National Academy of Sciences 114, no. 33 (July 31, 2017): E7018—E7027. http://dx.doi.org/10.1073/pnas.1706379114.

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Light signals regulate plant growth and development by controlling a plethora of gene expression changes. Posttranscriptional regulation, especially pre-mRNA processing, is a key modulator of gene expression; however, the molecular mechanisms linking pre-mRNA processing and light signaling are not well understood. Here we report a protein related to the human splicing factor 45 (SPF45) named splicing factor for phytochrome signaling (SFPS), which directly interacts with the photoreceptor phytochrome B (phyB). In response to light, SFPS-RFP (red fluorescent protein) colocalizes with phyB-GFP in photobodies. sfps loss-of-function plants are hyposensitive to red, far-red, and blue light, and flower precociously. SFPS colocalizes with U2 small nuclear ribonucleoprotein-associated factors including U2AF65B, U2A′, and U2AF35A in nuclear speckles, suggesting SFPS might be involved in the 3′ splice site determination. SFPS regulates pre-mRNA splicing of a large number of genes, of which many are involved in regulating light signaling, photosynthesis, and the circadian clock under both dark and light conditions. In vivo RNA immunoprecipitation (RIP) assays revealed that SFPS associates with EARLY FLOWERING 3 (ELF3) mRNA, a critical link between light signaling and the circadian clock. Moreover, PHYTOCHROME INTERACTING FACTORS (PIFs) transcription factor genes act downstream of SFPS, as the quadruple pif mutant pifq suppresses defects of sfps mutants. Taken together, these data strongly suggest SFPS modulates light-regulated developmental processes by controlling pre-mRNA splicing of light signaling and circadian clock genes.

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Bi, O., C. A. Anene, J. Nsengimana, M. Shelton, W. Roberts, J. Newton-Bishop, and J. R. Boyne. "SFPQ promotes an oncogenic transcriptomic state in melanoma." Oncogene 40, no. 33 (July 3, 2021): 5192–203. http://dx.doi.org/10.1038/s41388-021-01912-4.

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AbstractThe multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234, demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.

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Hewage, Thushara Welwelwela, Sofia Caria, and Mihwa Lee. "A new crystal structure and small-angle X-ray scattering analysis of the homodimer of human SFPQ." Acta Crystallographica Section F Structural Biology Communications 75, no. 6 (May 21, 2019): 439–49. http://dx.doi.org/10.1107/s2053230x19006599.

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Splicing factor proline/glutamine-rich (SFPQ) is an essential RNA-binding protein that is implicated in many aspects of nuclear function. The structures of SFPQ and two paralogs, non-POU domain-containing octamer-binding protein and paraspeckle component 1, from theDrosophilabehavior human splicing protein family have previously been characterized. The unusual arrangement of the four domains, two RNA-recognition motifs (RRMs), a conserved region termed the NonA/paraspeckle (NOPS) domain and a C-terminal coiled coil, in the intertwined dimer provides a potentially unique RNA-binding surface. However, the molecular details of how the four RRMs in the dimeric SFPQ interact with RNA remain to be characterized. Here, a new crystal structure of the dimerization domain of human SFPQ in theC-centered orthorhombic space groupC2221with one monomer in the asymmetric unit is presented. Comparison of the new crystal structure with the previously reported structure of SFPQ and analysis of the solution small-angle X-scattering data revealed subtle domain movements in the dimerization domain of SFPQ, supporting the concept of multiple conformations of SFPQ in equilibrium in solution. The domain movement of RRM1, in particular, may reflect the complexity of the RNA substrates of SFPQ. Taken together, the crystal and solution structure analyses provide a molecular basis for further investigation into the plasticity of nucleic acid binding by SFPQ in the absence of the structure in complex with its cognate RNA-binding partners.

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Kim, Tae Soo, Sung Bae Lee, and Hyen Sam Kang. "Glucose Repression of STA1 Expression Is Mediated by the Nrg1 and Sfl1 Repressors and the Srb8-11 Complex." Molecular and Cellular Biology 24, no. 17 (September 1, 2004): 7695–706. http://dx.doi.org/10.1128/mcb.24.17.7695-7706.2004.

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ABSTRACT In the yeast Saccharomyces diastaticus, expression of the STA1 gene, which encodes an extracellular glucoamylase, is negatively regulated by glucose. Here we demonstrate that glucose-dependent repression of STA1 expression is imposed by both Sfl1 and Nrg1, which serve as direct transcriptional repressors. We show that Nrg1 acts only on UAS1, and Sfl1 acts only on UAS2, in the STA1 promoter. When bound to its specific site, Sfl1 (but not Nrg1) prevents the binding to UAS2 of two transcriptional activators, Ste12 and Tec1, required for STA1 expression. We also found that Sfl1 contributes to STA1 repression by binding to the promoter and inhibiting the expression of FLO8, a gene that encodes a third transcriptional activator involved in STA1 expression. In addition, we show that the levels of Nrg1 and Sfl1 increase in glucose-grown cells, suggesting that the effects of glucose are mediated, at least in part, through an increase in the abundance of these repressors. NRG1 and SFL1 expression requires the Srb8-11 complex, and correspondingly, the Srb8-11 complex is also necessary for STA1 repression. However, our evidence indicates that the Srb8-11 complex does not associate with either the SFL1 or the NRG1 promoter and thus plays an indirect role in activating NRG1 and SFL1 expression.

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O’Brien, Gráinne, Lourdes Cruz-Garcia, Joanna Zyla, Natalie Brown, Rosemary Finnon, Joanna Polanska, and Christophe Badie. "Kras mutations and PU.1 promoter methylation are new pathways in murine radiation-induced AML." Carcinogenesis 41, no. 8 (October 24, 2019): 1104–12. http://dx.doi.org/10.1093/carcin/bgz175.

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Abstract Therapy-related and more specifically radiotherapy-associated acute myeloid leukaemia (AML) is a well-recognized potential complication of cytotoxic therapy for the treatment of a primary cancer. The CBA mouse model is used to study radiation leukaemogenesis mechanisms with Sfpi1/PU.1 deletion and point mutation already identified as driving events during AML development. To identify new pathways, we analysed 123 mouse radiation-induced AML (rAML) samples for the presence of mutations identified previously in human AML and found three genes to be mutated; Sfpi1 R235 (68%), Flt3-ITD (4%) and Kras G12 (3%), of which G12R was previously unreported. Importantly, a significant decrease in Sfpi1 gene expression is found almost exclusively in rAML samples without an Sfpi1 R235 mutation and is specifically associated with up-regulation of mir-1983 and mir-582-5p. Moreover, this down-regulation of Sfpi1 mRNA is negatively correlated with DNA methylation levels at specific CpG sites upstream of the Sfpi1 transcriptional start site. The down regulation of Sfpi1/PU.1 has also been reported in human AML cases revealing one common pathway of myeloid disruption between mouse and human AML where dysregulation of Sfpi1/PU.1 is a necessary step in AML development.

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Journal articles on the topic 'Sfp1'

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