Academic literature on the topic 'Scribble protein'
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Journal articles on the topic "Scribble protein"
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Liu, Hongbing, Lisa Golebiewski, Eugene C. Dow, Robert M. Krug, Ronald T. Javier, and Andrew P. Rice. "The ESEV PDZ-Binding Motif of the Avian Influenza A Virus NS1 Protein Protects Infected Cells from Apoptosis by Directly Targeting Scribble." Journal of Virology 84, no. 21 (August 11, 2010): 11164–74. http://dx.doi.org/10.1128/jvi.01278-10.
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ABSTRACT The NS1 protein from influenza A viruses contains a four-amino-acid sequence at its carboxyl terminus that is termed the PDZ-binding motif (PBM). The NS1 PBM is predicted to bind to cellular PDZ proteins and functions as a virulence determinant in infected mice. ESEV is the consensus PBM sequence of avian influenza viruses, while RSKV is the consensus sequence of human viruses. Currently circulating highly pathogenic H5N1 influenza viruses encode an NS1 protein with the ESEV PBM. We identified cellular targets of the avian ESEV PBM and identified molecular mechanisms involved in its function. Using glutathione S-transferase (GST) pull-down assays, we found that the ESEV PBM enables NS1 to associate with the PDZ proteins Scribble, Dlg1, MAGI-1, MAGI-2, and MAGI-3. Because Scribble possesses a proapoptotic activity, we investigated the interaction between NS1 and Scribble. The association between NS1 and Scribble is direct and requires the ESEV PBM and two Scribble PDZ domains. We constructed recombinant H3N2 viruses that encode an H6N6 avian virus NS1 protein with either an ESEV or mutant ESEA PBM, allowing an analysis of the ESEV PBM in infections in mammalian cells. The ESEV PBM enhanced viral replication up to 4-fold. In infected cells, NS1 with the ESEV PBM relocalized Scribble into cytoplasmic puncta concentrated in perinuclear regions and also protected cells from apoptosis. In addition, the latter effect was eliminated by small interfering RNA (siRNA)-mediated Scribble depletion. This study shows that one function of the avian ESEV PBM is to reduce apoptosis during infection through disruption of Scribble's proapoptotic function.
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Bonello, Teresa T., and Mark Peifer. "Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation." Journal of Cell Biology 218, no. 3 (December 31, 2018): 742–56. http://dx.doi.org/10.1083/jcb.201810103.
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Key events ranging from cell polarity to proliferation regulation to neuronal signaling rely on the assembly of multiprotein adhesion or signaling complexes at particular subcellular sites. Multidomain scaffolding proteins nucleate assembly and direct localization of these complexes, and the protein Scribble and its relatives in the LAP protein family provide a paradigm for this. Scribble was originally identified because of its role in apical–basal polarity and epithelial integrity in Drosophila melanogaster. It is now clear that Scribble acts to assemble and position diverse multiprotein complexes in processes ranging from planar polarity to adhesion to oriented cell division to synaptogenesis. Here, we explore what we have learned about the mechanisms of action of Scribble in the context of its multiple known interacting partners and discuss how this knowledge opens new questions about the full range of Scribble protein partners and their structural and signaling roles.
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Javorsky, Airah, Patrick O. Humbert, and Marc Kvansakul. "Structural Basis of the Avian Influenza NS1 Protein Interactions with the Cell Polarity Regulator Scribble." Viruses 14, no. 3 (March 11, 2022): 583. http://dx.doi.org/10.3390/v14030583.
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Scribble is a highly conserved regulator of cell polarity, a process that enables the generation of asymmetry at the cellular and tissue level in higher organisms. Scribble acts in concert with Disc-large (Dlg) and Lethal-2-giant larvae (Lgl) to form the Scribble polarity complex, and its functional dysregulation is associated with poor prognosis during viral infections. Viruses have been shown to interfere with Scribble by targeting Scribble PDZ domains to subvert the network of interactions that enable normal control of cell polarity via Scribble, as well as the localisation of the Scribble module within the cell. The influenza A virus NS1 protein was shown to bind to human Scribble (SCRIB) via its C-terminal PDZ binding motif (PBM). It was reported that the PBM sequence ESEV is a virulence determinant for influenza A virus H5N1 whilst other sequences, such as ESKV, KSEV and RSKV, demonstrated no affinity towards Scribble. We now show, using isothermal titration calorimetry (ITC), that ESKV and KSEV bind to SCRIB PDZ domains and that ESEV unexpectedly displayed an affinity towards all four PDZs and not just a selected few. We then define the structural basis for the interactions of SCRIB PDZ1 domain with ESEV and ESKV PBM motifs, as well as SCRIB PDZ3 with the ESKV PBM motif. These findings will serve as a platform for understanding the role of Scribble PDZ domains and their interactions with different NS1 PBMs and the mechanisms that mediate cell polarity within the context of the pathogenesis of influenza A virus.
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Hegde, Shailaja N., Mark J. Althoff, Ramesh C. Nayak, Ashley M. Wellendorf, Fatima Mohmoud, Gang Huang, Yi Zheng, Maria T. Diaz-Meco, Jorge Moscat, and Jose A. Cancelas. "Basal Polarity Complex Scribble Is Required for Leukemic Initiation and Propagation through Negative Regulation of Apical Polarity Complex Activator Cdc42 and Hypoxia Inducing Factor-1α." Blood 132, Supplement 1 (November 29, 2018): 551. http://dx.doi.org/10.1182/blood-2018-99-118919.
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Abstract Despite the introduction of tyrosine kinase inhibitor and CAR-T cell therapies, the prognosis for Ph+ and Ph-like acute lymphoblastic leukemia remains poor. In the present study, we show the role of the Scribble protein in both lymphoid and myeloid leukemogenesis. The polarity protein Scribble is a member of the basal polarity complex, which is down-regulated in many cancers, suggesting a possible tumor suppressor role, especially in so-called cancer initiating cells. Its effect and mechanisms of activity in leukemic cell fate along with its potential activity on leukemic initiating cells have only been recently started to elucidated. Using interferon-responsive inducible (Mx1-Cre) Scribble-deficient mice, we have characterized the role of Scribble in both retroviral transduction, transplantation animal models and binary, inducible stem cell initiated (Scl-tTA/TRE-BCR-ABL) serial propagation models of BCR-ABL induced leukemia. We found that Scribble expression is upregulated at both transcriptional and translational levels in p210- or p190-BCR-ABL induced leukemic progenitors. In vitro, leukemic colony formation was impaired in Scribble deficient leukemic progenitors (~48% reduction; p≤ 0.05, compared to Wt leukemic progenitors) demonstrating that Scribble is important for leukemogenesis. In vivo, the deletion of Scribble abrogates the development of myeloproliferative disease induced by p210-BCR-ABL (median survival: 70 vs 47 days in Scribble deficient and Wt chimeric mice, respectively; p≤0.05); and significantly impairs B-cell lymphoid leukemogenesis induced by p190-BCR-ABL (median survival: 80 vs 60 days for Scribble deficient and Wt chimeric animals, respectively). Mechanistically, BCR-ABL activates the apical polarity regulator Cdc42 in leukemic progenitors and this activation is inhibited by the deficiency of Scribble. The deficiency of Cdc42 does not impair leukemogenesis but the combined deficiency of Cdc42 and Scribble restores the in vivo survival (median survival: 47 days, p≤0.01 compared to Scribble deficient mice) in chimeric p190-BCR-ABL+ leukemic mice to levels similar to wild-type leukemic cells. These data indicate that Scribble-deficient leukemogenesis is dependent on oncogene induced Cdc42 activity in lymphoid progenitors. Furthermore, Scribble deficiency in leukemic progenitors increases the activation of the AMPK/mTORC1 signaling pathway and the protein expression and transcriptional activity of its downstream effector hypoxia-inducing factor-1α (HIF-1α). HIF-1α silencing by constitutive shRNA expression or inducible deletion in Scribble deleted B-lymphoid leukemic cells restored leukemic progenitor clonogenic efficiency (CFU average: 52 vs 110 per 1,000 B220+/EGFP+ BM cells, in Scribble and double Scribble/HIF-1α deficient, respectively; p≤0.01) and B-lymphoid leukemogenesis in vivo (median survival of 62 days; p≤0.05 compared with Scribble deficient chimeric animals). In addition, double deficiency of Scribble and HIF-1α restored AMPK/mTORC1 signaling to Wt leukemic levels. This data indicates that Scribble is a negative regulator of HIF-1α expression and activity, and the restoration of HIF-1α expression and activity to normal leukemic levels is necessary to restore leukemogenesis. Altogether, our data indicates that Scribble is a positive regulator of oncogenesis in leukemic progenitors, in vitro and in vivo, through Cdc42 and HIF-1α activities. Disclosures No relevant conflicts of interest to declare.
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Pieczynski, Jay, and Ben Margolis. "Protein complexes that control renal epithelial polarity." American Journal of Physiology-Renal Physiology 300, no. 3 (March 2011): F589—F601. http://dx.doi.org/10.1152/ajprenal.00615.2010.
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Establishment of epithelial apicobasal polarity is crucial for proper kidney development and function. In recent years, there have been important advances in our understanding of the factors that mediate the initiation of apicobasal polarization. Key among these are the polarity complexes that are evolutionarily conserved from simple organisms to humans. Three of these complexes are discussed in this review: the Crumbs complex, the Par complex, and the Scribble complex. The apical Crumbs complex consists of three proteins, Crumbs, PALS1, and PATJ, whereas the apical Par complex consists of Par-3, Par-6, and atypical protein kinase C. The lateral Scribble complex consists of Scribble, discs large, and lethal giant larvae. These complexes modulate kinase and small G protein activity such that the apical and basolateral complexes signal antagonistically, leading to the segregation of the apical and basolateral membranes. The polarity complexes also serve as scaffolds to direct and retain proteins at the apical membrane, the basolateral membrane, or the intervening tight junction. There is plasticity in apicobasal polarity, and this is best seen in the processes of epithelial-to-mesenchymal transition and the converse mesenchymal-to-epithelial transition. These transitions are important in kidney disease as well as kidney development, and modulation of the polarity complexes are critical for these transitions.
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Sun, Yu, Mytyl Aiga, Eileen Yoshida, Patrick O. Humbert, and Shernaz X. Bamji. "Scribble Interacts with β-Catenin to Localize Synaptic Vesicles to Synapses." Molecular Biology of the Cell 20, no. 14 (July 15, 2009): 3390–400. http://dx.doi.org/10.1091/mbc.e08-12-1172.
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An understanding of how synaptic vesicles are recruited to and maintained at presynaptic compartments is required to discern the molecular mechanisms underlying presynaptic assembly and plasticity. We have previously demonstrated that cadherin–β-catenin complexes cluster synaptic vesicles at presynaptic sites. Here we show that scribble interacts with the cadherin–β-catenin complex to coordinate vesicle localization. Scribble and β-catenin are colocalized at synapses and can be coimmunoprecipitated from neuronal lysates, indicating an interaction between scribble and β-catenin at the synapse. Using an RNA interference approach, we demonstrate that scribble is important for the clustering of synaptic vesicles at synapses. Indeed, in scribble knockdown cells, there is a diffuse distribution of synaptic vesicles along the axon, and a deficit in vesicle recycling. Despite this, synapse number and the distribution of the presynaptic active zone protein, bassoon, remain unchanged. These effects largely phenocopy those observed after ablation of β-catenin. In addition, we show that loss of β-catenin disrupts scribble localization in primary neurons but that the localization of β-catenin is not dependent on scribble. Our data supports a model by which scribble functions downstream of β-catenin to cluster synaptic vesicles at developing synapses.
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Althoff, Mark J., Ramesh C. Nayak, Shailaja Hegde, Ashley M. Wellendorf, Fatima Mohmoud, Maria T. Diaz-Meco, Jorge Moscat, and Jose A. Cancelas. "Scribble Controls HSC Self-Renewal through Polarity-Dependent Activation of the Hippo Signaling Pathway." Blood 130, Suppl_1 (December 7, 2017): 710. http://dx.doi.org/10.1182/blood.v130.suppl_1.710.710.
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Abstract Search of molecular targets to expand functional hematopoietic stem cells (HSC) for transplantation and hematological cancer therapy remains paramount, particularly when manipulation of cellular quiescence is required. HSC are highly quiescent cells with the ability to rapidly enter the cell cycle in response to microenvironment cues and divide through changes in their polarity. Despite cellular polarity being one of the most basic properties of all living cells, the role that polarity regulators have on polarization and function of HSC remains controversial. Scribble, of the Scribble Polarity Complex, controls the spatial organization of intracellular proteins and negatively regulates the cell cycle. By using a combination of constitutive and inducible hematopoietic-specific Scribble-deficient animal models, hematopoietic reconstitution assays, structure-function mutants of Scribble and intracellular protein trafficking analysis, we identified the functional relevance of Scribble in HSC activity. We observed that Scribble is polarized in HSC and deletion of Scribble leads to a ~ 50% reduction in the bone marrow (BM) HSC population (p<0.001). Scribble-deficient HSC are less quiescent (G0: 93 vs 88%, p<0.05; S/G2/M 4 vs 10%, for WT and KO, respectively, p<0.01) and contain ~70% reduction of dormant, long-term HSC (p<0.01). This data indicates that Scribble is required to maintain HSC quiescence. Functionally, stroma-dependent long-term BM cultures revealed that Scribble-deficient BM contains a ~ 60% reduction in the number of early cobblestone area-forming cells (CAFC) while their content of late (28-35 day) CAFC (primitive progenitors/HSC) is 3-5 fold increased. Serial transplantation experiments demonstrated that Scribble-deficient BM HSC have increased competitive repopulating potential (46% vs 90% BM chimerism for WT and KO BM from tertiary recipient mice, respectively, p<0.001). Moreover, deletion of hematopoietic Scribble protects mice from 5-fluorouracil (5-FU)-mediated hematopoietic exhaustion and death by BM aplasia (>30 days median survival vs 16 days for KO mice, p<0.001). This set of functional data indicates that Scribble deficient HSC show enhanced long-term self-renewal capacity in stroma-dependent cultures and in vivo following transplantation or chemotherapeutic stress without the development of stem cell exhaustion or leukemia. Comparative transcriptional analysis of Scribble-deficient and WT HSC identified transcriptional regulation of the Hippo-dependent signaling pathway. We observed that Yap1 is polarized in a Scribble-dependent manner within WT HSC and co-localizes in the cytoplasm with the active form of the upstream inhibitory kinase, Lats1. Notably, deletion of Scribble in HSC leads to a disruption of the phosphorylated Lats1/Yap1 complex resulting in Yap1 translocation to the nucleus. Subsequently, cytoplasmic polarization of Yap1 can be restored when Scribble-deficient HSC are rescued with full length or PDZ domain containing mutants of Scribble. Expression of the N-terminus leucine-rich repeat (LRR) domain of Scribble successfully restored activation of Lats1 as well as phosphorylated Lats1 co-localization with Scribble, however, was not sufficient to prevent Yap1 translocation. Combined deletion of Yap1 and Taz using an inducible hematopoietic-specific model generates hematopoietic stem and progenitor cells (HSC/P) with enhanced cellular proliferation (HSC G0: 88 vs. 58%, p<0.0001; G1: 6 vs. 25%, p<0.0001; S/G2/M 6 vs. 18%, p<0.0001 for WT controls and Yap1/Taz double deficient BM, respectively) leading to an increase in colony forming units and early CAFC potential (2 and 3 fold respectively; p<0.0001). Yap1/Taz double KO HSC are prone to exhaustion evidenced by their inability to regenerate murine hematopoiesis after serial administration of 5-FU (12 days median survival vs 20 days for WT control mice, p<0.001). Triple deficiency of Scribble, Yap1 and Taz restores the effect of both Scribble and Yap1/Taz deficiencies to a normal hematopoietic response after myeloablation. Altogether, this data identifies Scribble as a negative regulator of cell cycle entry and self-renewal of HSC, and provides compelling evidence of key polarity and signaling programs used to maintain HSC quiescence that can be utilized as novel targets to improve HSC based transplantations and hematological cancer therapies. Disclosures No relevant conflicts of interest to declare.
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Fenner, Annette. "Scribble complex protein deficiency promotes prostate tumors in vivo." Nature Reviews Urology 8, no. 12 (November 15, 2011): 644. http://dx.doi.org/10.1038/nrurol.2011.167.
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Singh, Abhishek K., Mark J. Althoff, Saimul Islam, Ashley M. Wellendorf, and Jose A. Cancelas. "Scribble Is a Negative Regulator of Interferon-I Dependent Notch1 Activation in Adult Hematopoietic Stem Cells and Progenitors." Blood 138, Supplement 1 (November 5, 2021): 299. http://dx.doi.org/10.1182/blood-2021-151046.
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Abstract Hematopoietic stem cells (HSC) are highly quiescent cells with the ability to rapidly enter cell cycle and differentiate through changes in their polarity and the disposition of intracellular molecular fate determinants in response to microenvironment (ME) cues. Interferons type 1 (IFN-I) are ME cytokines produced during the physiological response mounted to combat a viral infection. In bone marrow hematopoiesis, IFN-I induces activation and proliferation of HSC. Clinically, patients treated with IFN-I, as well as individuals suffering from IFN-I associated chronic disease, often exhibit sustained hematological cytopenias and HSC failure. The precise molecular mechanisms that govern HSC behavior in response to IFN-I are still unclear. Our data highlights that Scribble deficient HSC are less sensitive to IFN-I mediated activation. By using hematopoietic specific deletion of Scribble in murine hematopoiesis (Vav-Cre;Scribble KO); we demonstrated that Scribble deficient LSK CD150 +/CD48 - HSC are less responsive to polyinositide-polycytidine (pI:C) induced IFN-I mediated activation and retain cellular quiescence (G0:45±5.4% vs 63±2.7% in WT and Scribble KO, respectively, p<0.05). IFN-I induced upregulation of Sca-1 expression was also significantly hampered in Scribble deficient HSC. Functionally, serial transplantation experiments demonstrated that in response to poly I:C, Scribble deficient HSC display increased competitive repopulating potential (26±1.3% vs 38±1.2% BM chimerism for WT and KO BM in secondary recipients and 38±2.5% vs 48±2.7% BM chimerism in tertiary recipients, p<0.01). The maintenance of cellular quiescence and function for Scribble deficient HSC are independent of canonical IFN-I driven STAT-1 signaling, as we report no differences in STAT-1 activation, nuclear translocation or the expression of STAT-1 canonical target genes in response to pI:C. Unsupervised transcriptomics analysis of Scribble-deficient HSC supported dysregulation of Notch signaling. Furthermore, Scribble deficiency in non-activated LSK HSC and progenitors (HSPC) was associated with constitutive activation and cleavage of Notch1 (Notch1 ICD;~3 fold) at levels comparable to IFN-I mediated activation of WT HSPC. However, Scribble deficient HSPC did not exhibit further Notch1 cleavage activation upon in vivo IFN-I induction. Pharmacological in vivo γ-secretase inhibition (YO-01027) prevented the protective effect of Scribble deficiency on IFN-I dependent loss of HSC quiescence. These data indicate that Notch1 activation, and subsequent cleavage, is indispensable for Scribble deficient HSC quiescence in response to IFN-I. Active Cdc42 is a critical regulator of HSC quiescence and fate, and previous studies have demonstrated that Scribble controls HSC asymmetric division potential and fate through the PDZ mediated scaffolding of cytosolic Yap1 with activated Cdc42 (Cdc42-GTP). Next to determine whether poly I:C mediated Notch1 cleavage linked with Cdc42 activity, we analyzed the protein interactions between cleaved Notch1 and Cdc42-GTP in relation with Scribble. Our findings revealed that Scribble associates with non-cleaved, membrane bound Notch but upon in vivo IFN-I induction Notch1 is cleaved, activated and translocates with Scribble-free, activated Cdc42 to the nucleus of HSC. Deletion of HSC Scribble associated with a reduced (~45%, p<0.001) proximity interaction between cleaved Notch1 and Cdc42-GTP. Collectively our findings identify that Scribble controls IFN-I mediated HSPC activation through induction of Notch1 cleavage and Cdc42 activity, and highlight such interaction as a new potential target to dampen inflammation driven HSC exhaustion. Disclosures Cancelas: Cerus Co: Research Funding; TerumoBCT: Research Funding; Hemanext: Membership on an entity's Board of Directors or advisory committees, Research Funding; Cytosorbents Inc: Research Funding; Fresenius-Kabi LLC: Research Funding; Westat Inc: Research Funding; Vascular Solutions Inc.: Research Funding; Hemerus LLC: Research Funding; University of South Florida/MEQU Inc: Research Funding.
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Choi, Jongho, Regina B. Troyanovsky, Indrajyoti Indra, Brian J. Mitchell, and Sergey M. Troyanovsky. "Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex." Journal of Cell Biology 218, no. 7 (May 30, 2019): 2277–93. http://dx.doi.org/10.1083/jcb.201804201.
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The basolateral protein Scribble (Scrib), a member of the LAP protein family, is essential for epithelial apicobasal polarity (ABP) in Drosophila. However, a conserved function for this protein in mammals is unclear. Here we show that the crucial role for Scrib in ABP has remained obscure due to the compensatory function of two other LAP proteins, Erbin and Lano. A combined Scrib/Erbin/Lano knockout disorganizes the cell–cell junctions and the cytoskeleton. It also results in mislocalization of several apical (Par6, aPKC, and Pals1) and basolateral (Llgl1 and Llgl2) identity proteins. These defects can be rescued by the conserved “LU” region of these LAP proteins. Structure–function analysis of this region determined that the so-called LAPSDb domain is essential for basolateral targeting of these proteins, while the LAPSDa domain is essential for supporting the membrane basolateral identity and binding to Llgl. In contrast to the key role in Drosophila, mislocalization of Llgl proteins does not appear to be critical in the scrib ABP phenotype.
Dissertations / Theses on the topic "Scribble protein"
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Christofakis, Steven. "SCRIBBLE: A POTENTIAL DUAL KINASE INHIBITOR." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/72.
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Extracellular signal-regulated kinases (ERKs) modulate cellular activities in response to extracellular stimuli and play important biological roles. Thus, perturbed kinase pathways induce pathological conditions, such as tumor development. Rit, a novel member of the Ras family GTPases, activase ERK6, and its over-expression confers tumorigenicity. We hypothesized the presence of scaffolding molecules specific to ERK6, similar to other known MAP kinases. We performed yeast two-hybrid assays using ERK6 as bait, and Scribble was identified as a binding partner. Scribble contains 16 LRR domains and four PDZ domains. We performed immunoprecipitation (IP) assays and discovered ERK2 as another binding partner. Surprisingly, no interaction was observed with the highly homologous MAP kinase, ERK1. No other representative kinases showed binding capabilities with Scribble. IP data confirmed that both ERK2 and ERK6 bind to Scribble through its LRR and PDZ domains. Deletion of ten aminoi acids from the C-terminus of ERK2 and ERK6 abolished these interactions. In vitro kinase assays indicated the kinase suppressing ability of Scribble. Focus formation assays were performed with RitQ79L and H-RasV12 as constitutive activators of ERK6 and ERK2, respectively, in the presence of Scribble. Results confirmed the role of Scribble as a tumor suppressor.
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Adoki, Samson. "Involvement of scribble protein in breast cancer invasion and metastasis." Thesis, University of Essex, 2016. http://repository.essex.ac.uk/17655/.
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A common feature of cancer cells is the loss of cell polarity. Scribble is a cell polarity protein with an unknown mechanism for its role in tumour suppression. Changes in the phosphorylation pattern of four serine sites at the C-terminal of scribble, implicate scribble in breast cancer invasion and metastasis. This was due to CD74 overexpression in lymph node metastatic triple negative breast cancers. Investigating how changes in serine phosphorylation status at these sites affect the regulation of invasion and metastasis in breast cancer was the focus of this study. These sites were mutated by site-directed mutagenesis to generate mutant scribble genes grouped into A-mutants and D-mutants, based on the amino acid change to the serine sites to mimic unphosphorylated and phosphorylated scribble, respectively. Widefield and confocal bioimaging of the expression and localization of these mutants in cell line HEK293T revealed good expression but varied localization to cytoskeletal elements, intercellular contact site, microtubules, centrosome and vesicles. Wound healing, MTT and flow cytometry assays were conducted on HEK293T transfected with these mutant genes to study how their expression affected cell migration, proliferation and the cell cycle, respectively. Notable differences emerged: 1.) A-mutants migrated more than D-mutants. 2.) D-mutants proliferated more than A-mutants and 3.) There were significantly more D-mutant expressing cells in the G2 phase of the cell cycle. Protein interaction study was also conducted. The binding partners of S[1306+1309]A and S[1306+1309]D mutants of scribble were captured and analysed by Co-IP and mass spectrometry. Bioinformatics analysis identified the pathways these binding proteins were significantly involved in: S[1306+1309]A binding partners were involved in cell migration via regulation of actin cytoskeleton pathway but contribute to intercellular adhesion via the tight junction pathway. S[1306+1309]D binding partners were involved in the TSH signalling and cell cycle pathways. The results show a significant possibility that unphosphorylated and phosphorylated hScrib support cell invasion and cell proliferation, respectively, and that these processes are antagonistic.
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Wan, Shan [Verfasser], and Peter [Akademischer Betreuer] Angel. "Impact of the cell polarity protein Scribble on liver cancer formation and progression / Shan Wan ; Betreuer: Peter Angel." Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1178010589/34.
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Blanc, Jean-Michel. "Etude moléculaire et fonctionnelle des assemblages multiproteiques impliquant les proteines de la polarité planaire Vangl2 et Scribble1." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4131.
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Il existe de nombreux mécanismes impliqués dans le développement des tissus qui nécessitent que des cellules ou des groupes de cellules s’orientent et se polarisent. Les protéines de la voie de la polarité planaire (PP) s’associent pour former des complexes à la membrane et créer des asymétries proximo-distale. Vangl2 et Scrib1 ont été identifiés comme les deux premiers gènes impliqués dans la PP chez les mammifères. Lors de ma thèse, je me suis intéressé à ces deux protéines et à certains des complexes dans lesquelles elles sont impliquées. Dans un premier temps, nous avons montré l’implication directe de Scribble1 dans le trafic après endocytose des récepteurs NMDA. Scrib1 interagit avec les récepteurs NMDA grâce à ses domaines PDZ. Scribble1 peut interagir avec le complexe AP2 qui intervient dans l’endocytose des récepteurs. Cette étude a permis de définir un nouveau mécanisme dans lequel Scrib1 régule la quantité de récepteurs NMDA à la membrane et donc participe à la plasticité synaptique. Vangl2 est l’une des protéines transmembranaires les plus en amont de la voie de la PP. Nous avons identifié un nouveau partenaire nommé "Axin Interaction partner and Dorsalization Antagonist" (AIDA). Nous avons montré, par double hybride en levure et pull down, l’interaction de Vangl2 avec les deux isoformes de AIDA et leur colocalisation en COS7 et neurones. Ensemble, ces données présentent AIDA comme un très bon candidat pour le maintien de Vangl2 aux jonctions adhérentes et/ou pour son adressage à la membrane. Ces études nous ont permis d’améliorer notre compréhension des mécanismes impliquant les protéines de la polarité planaireThere are many mechanisms involved in the development of tissues that require cells or groups of cells orient and polarize. The proteins of the planar cell polarity (PCP) combine to form complexes with the membrane and create proximal-distal asymmetries. Vangl2 and Scrib1 have been identified as the first two genes involved in the PCP in mammals. In this study, I am interested in these two proteins and some of the complex in which they are involved. At first, using techniques of biochemistry, cell biology and biophysics, we showed the direct involvement of Scribble1 in traffic after endocytosis of NMDA receptors. Scrib1 interacts with NMDA receptors through its PDZ domains. Due to this binding motif between PDZ1 and PDZ2 of Scrib1, it can interact with the AP2 complex which is involved in receptor endocytosis. This study has identified a new mechanism in which Scrib1 regulates the amount of NMDA receptors on the membrane and is therefore involved in synaptic plasticity. Vangl2 is a transmembrane protein of the most upstream of the PCP pathway. We have identified a new partner named "Axin Interaction partner and Dorsalization Antagonist" (AIDA). We have shown, by yeast two-hybrid and pull down the interaction of Vangl2 with two isoforms of AIDA and collocation in COS7 and neurons. Together, these data show AIDA as a very good candidate for maintaining Vangl2 to adherens junctions and/or its membrane targeting. These studies have allowed us to improve our understanding of the mechanisms involving the planar polarity proteins
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Richier, Lindsay. "THE NITRIC OXIDE SYNTHASE ADAPTOR PROTEIN (NOS1AP) ASSOCIATES WITH SCRIBBLE AND REGULATES DENDRITIC SPINE DEVELOPMENT." 2009. http://hdl.handle.net/10222/12823.
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In a targeted proteomic screen to identify polarity protein complexes, a number of Scribble (Scrib) -associating proteins were identified; of particular interest was the Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP). NOS1AP contains an N-terminal phosphotyrosine binding (PTB) domain and a C-terminal PSD-95/Dlg homology/ZO-1 (PDZ) binding motif that associates with neuronal NOS (NOS1). We show that the PTB domain of NOS1AP associates with the fourth PDZ domain of Scrib. We identified NOS1AP binding partners including three key regulators of dendritic spine formation, beta-Pix, Git1, and PAK, which require Scrib to associate with NOS1AP. Overexpression of NOS1AP in cultured hippocampal neurons increases dendritic protrusions, a process dependent on the PTB domain. The increase in dendritic protrusions can be blocked by the co-expression of a dominant negative Rac construct. NOS1AP, and the PTB domain of NOS1AP influence Rac activity. Together these data suggest that Scrib and NOS1AP function as important scaffolding proteins in the mammalian synapse and that NOS1AP functions in the dendritic spine by influencing Rho GTPase activity.
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Gramates, L. Sian. "Cloning and characterization of GUKHolder, a novel synaptically expressed protein that interacts with Discs -Large and SCRIBBLE at the Drosophila neuromuscular junction." 2001. https://scholarworks.umass.edu/dissertations/AAI3027203.
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Synaptic transmission between a neuron and its target is crucially dependent upon the precise spatial arrangement of proteins in the pre- and postsynaptic apparatus. PDZ domain-containing proteins such as the Drosophila tumor suppressor Discs-Large (DLG) play critical roles in synapse maturation by regulating the assembly of synaptic protein complexes. DLG is composed of a number of modular domains, including three PDZ-domains, an SH3 domain and an enzymatically inactive Guanylate Kinase-like (GUK) domain. Previous studies have shown that the PDZ domains of DLG mediate clustering of Shaker K+ channels and of the cell adhesion molecule Fasciclin II. However, the function of the GUK domain has been unclear. To understand the role of the GUK domain, we carried out a yeast-two hybrid screen for interacting partners of the DLG GUK domain. This screen lead to the identification of a novel synapse-associated protein, GUKHolder (GUKH). GUKH is a 1044 amino acid protein with a molecular weight of 110 kDa. Its sequence includes a GUK-holding domain, a region homologous to the C-terminal of the long isoform of Kelch, a WH1-like domain, and a PDZ-domain binding motif. These latter two features suggest that GUKH may interact not only with DLG, but also with other proteins, including proteins containing PDZ domains. GUKH is expressed at the larval neuromuscular junction and at epithelial cell borders in partial colocalization with DLG. Further, DLG can be co-immunoprecipitated with GUKH from Drosophila extracts, indicating an in vivo interaction between the two proteins. GUKH has also been shown to interact directly with SCRIBBLE (SCRIB), another synaptically expressed PDZ-domain protein known to have a genetic interaction with dlg in epithelial tissues. Synaptic SCRIB immunoreactivity is mislocalized in both gukh and dlg mutants. gukh, scrib, and dlg mutants all exhibit synaptic bouton defects at the ultrastructural level. These data indicate that all three proteins are required for proper synapse maturation, and support a model that the three proteins exist in a tripartite complex, with GUKH forming a link between the other two proteins, and further, between the protein scaffolds organized by the two proteins.
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Packard, Mary C. "Formation and plasticity of glutamatergic synapses: Characterization of the roles of beta-amyloid precursor protein, scribble, and wingless at the Drosophila neuromuscular junction." 2004. https://scholarworks.umass.edu/dissertations/AAI3136762.
Full textAbstract:
The flow of information through neuronal circuits relies on the ability of neurons to form synaptic connections with specific temporal and spatial properties. These properties are not static but have the ability to change, allowing synaptic connections to be strengthened or weakened. It is this plastic nature of synapses that is central to higher order processes such as learning and memory. However, major gaps remain in our understanding of this process. Throughout my dissertation work I have examined mechanisms of a form of structural synaptic plasticity by analyzing the roles of a variety of proteins that we have found serve to regulate the formation and maintenance of glutamatergic synapses at the Drosophila NMJ. These proteins include APPL, the Drosophila homolog of Alzheimer's disease-associated β-Amyloid Precursor Protein (APP), the tumor suppressor protein Scribble (Scrib), the secreted signaling molecule Wingless (Wg), and the cell adhesion molecule Fasciclin II (FasII). In this work, in collaboration with members of the labs of Dr. Vivian Budnik, Dr. Kalpana White, and Dr. Susan Cumberledge, I have demonstrated that Wingless (Wg) provides a secreted signal that is required to initiate the formation of pre- and postsynaptic structures. Further, I have also demonstrated that once synapse formation is initiated, presumably by Wg signaling, APPL regulates synaptic bouton proliferation. This process also involves signaling by FasII, a protein required for synapse maintenance, and growth. Moreover, I have also demonstrated that Scrib is a scaffolding protein that plays a key role at these synapses in influencing neurotransmitter release.
Books on the topic "Scribble protein"
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Jarmoszko, ABJarKids. Password Log Book with Phone Call and Notes Space Alphabetical Tabs Small Pocket Journal Size 6x9 Inches with a Pattern of Cat Scribbles Internet Password Organizer Notebook: Logbook to Protect Usernames Email Address. Independently Published, 2021.
Find full textBook chapters on the topic "Scribble protein"
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Su, Wen-Hui, Dolores D. Mruk, Elissa W. P. Wong, Wing-Yee Lui, and C. Yan Cheng. "Polarity Protein Complex Scribble/Lgl/Dlg And Epithelial Cell Barriers." In Advances in Experimental Medicine and Biology, 149–70. New York, NY: Springer New York, 2013. http://dx.doi.org/10.1007/978-1-4614-4711-5_7.
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Dakessian, Arek, Célia Hassani, and Sarah Shmaitilly. "‘The people awoke awake’: observations from Beirut’s walls in the 17 October moment." In Arts, Culture and Community Development, 51–72. Policy Press, 2021. http://dx.doi.org/10.1332/policypress/9781447340508.003.0004.
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In this chapter we reflect on street art in Beirut during the October 17 revolutionary moment, when a decades-long accumulation of social, political and economic ills culminated in unprecedented and sustained protest across Lebanon. Through our engagement with a series of murals, stencils and graffiti that emerged on Beirut’s walls around October 17, as well as numerous scribbles by anonymous citizens around these more formal works of art and on random public surfaces, we argue that street art might have mediated the formation of citizen subjectivities by ‘making public’ conversations, contestations and reflections previously restricted to the private and intimate spaces of home and family.
Conference papers on the topic "Scribble protein"
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Feigin, Michael E., Avi Z. Rosenberg, Robert D. Cardiff, and Senthil K. Muthuswamy. "Abstract 920: Mislocalization of the polarity protein Scribble promotes tumorigenesis in the mouse mammary gland." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-920.
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Wan, Shan, Anne-Sophie Meyer, Sofia Weiler, Teresa Lutz, Stephanie Roessler, Peter Schirmacher, Federico Pinna, and Kai Breuhahn. "Abstract 1130: Subcellular localization of the cell polarity protein Scribble defines its oncogenic activity in hepatocellular carcinoma." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1130.
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Lim, Krystle YB, Sofia Caria, Colin M. House, Nathan J. Godde, Allison J. Ogden, Patrick O. Humbert, and Marc Kvansakul. "Abstract C203: Cracking the (ultra)structural biology of Scribble to understand its role as a cell polarity regulator and tumor suppressor protein." In Abstracts: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; November 5-9, 2015; Boston, MA. American Association for Cancer Research, 2015. http://dx.doi.org/10.1158/1535-7163.targ-15-c203.
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