Affinage

SCRIB

Protein scribble homolog · UniProt Q14160

Length
1655 aa
Mass
177.7 kDa
Annotated
2026-04-28
69 papers in source corpus 33 papers cited in narrative 33 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCRIB is a multi-domain scaffold protein that organizes polarity, signaling, and adhesion complexes at cell-cell junctions and the cell cortex to coordinate planar cell polarity, directed cell migration, epithelial apico-basal polarity, and tumor suppression. Through its PDZ domains and leucine-rich repeats, SCRIB nucleates distinct complexes—βPIX/GIT/PAK for Rac1/Cdc42-dependent polarized migration (PMID:17081755, PMID:18716323), MRAS/SHOC2/PP1 for ERK-MAPK suppression via competition for PP1 (PMID:24211266), SHROOM/ROCK1 for apical contractility (PMID:37930352), SLC3A2/LLGL2/SLC7A5 for amino acid transporter membrane localization (PMID:35501367), and cortical actomyosin clusters via myosin-1c for adherens junction stability (PMID:42043432)—while also maintaining integrin α5 surface levels by blocking Rab7a-mediated lysosomal degradation (PMID:23362312). SCRIB functions genetically within the planar cell polarity pathway through epistatic interaction with Vangl2, and its loss-of-function causes craniorachischisis in mice and is linked to human neural tube defects (PMID:12724779, PMID:12499390, PMID:22095531). High-risk HPV E6 oncoprotein targets SCRIB's PDZ domains for E6AP-mediated ubiquitin-dependent degradation, disrupting tight junctions (PMID:11027293).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2000 High

    Establishing SCRIB as a target of oncogenic HPV resolved how E6 disrupts epithelial junctions: E6 uses a PDZ-binding motif to recruit E6AP ubiquitin ligase for SCRIB degradation, directly linking a polarity protein to viral oncogenesis.

    Evidence In vitro ubiquitination reconstitution, Co-IP of E6AP-E6-hScrib complex, ZO-1 localization in MDCK cells

    PMID:11027293

    Open questions at the time
    • Whether endogenous SCRIB turnover uses the same ubiquitin pathway outside HPV infection
    • Whether other PDZ-containing polarity proteins are similarly targeted
  2. 2003 High

    Genetic studies in mouse established SCRIB as a core component of the mammalian planar cell polarity pathway: Scrib mutation causes craniorachischisis and stereociliary polarity defects, and Scrib genetically interacts with the PCP gene Vangl2.

    Evidence ENU mutagenesis and positional cloning in mouse, double-heterozygote genetic epistasis with Vangl2, SEM of cochlear hair cells

    PMID:12499390 PMID:12724779

    Open questions at the time
    • Whether SCRIB physically binds Vangl2 or acts in a parallel arm of PCP signaling
    • The biochemical mechanism by which SCRIB transduces PCP signals in mammals
  3. 2003 High

    Work in Drosophila neuroblasts demonstrated that Scrib (with Dlg and Lgl) is required for asymmetric cell division, positioning SCRIB as a regulator of cell fate beyond epithelial polarity.

    Evidence Drosophila loss-of-function genetics, immunofluorescence and time-lapse imaging of neuroblast divisions

    PMID:12545176

    Open questions at the time
    • Whether Scrib, Dlg, and Lgl act as a single complex or in parallel in neuroblasts
    • Mechanism of apical cortical enrichment of Scrib
  4. 2006 High

    The discovery that SCRIB recruits βPIX to the leading edge to activate Cdc42 and Rac1 identified the first molecular mechanism by which SCRIB directs cell migration, establishing SCRIB as a signaling scaffold rather than a passive structural component.

    Evidence siRNA knockdown, dominant-negative constructs, Co-IP, Cdc42/Rac activity assays in astrocyte scratch-wound migration

    PMID:17081755 PMID:18716323

    Open questions at the time
    • How SCRIB itself is polarized to the leading edge
    • Whether the SCRIB-βPIX-GIT-PAK complex composition varies by cell type
  5. 2011 High

    Conditional knockout in mouse prostate showed that Scrib functions as a dose-dependent tumor suppressor by negatively regulating MAPK/ERK signaling, and cooperates with oncogenic Kras to drive cancer progression, linking polarity loss to a specific oncogenic signaling cascade.

    Evidence Conditional Cre-lox knockout mouse, MAPK signaling assays, genetic epistasis with KrasG12D

    PMID:21965329

    Open questions at the time
    • The precise biochemical step at which Scrib suppresses MAPK—resolved later by PP1 competition mechanism
    • Whether Scrib tumor suppression is tissue-specific
  6. 2011 Medium

    Identification of SCRIB missense variants in human craniorachischisis patients, which impair plasma membrane trafficking without disrupting protein-protein interactions, provided the first direct evidence linking SCRIB mutations to human neural tube defects.

    Evidence Patient sequencing, subcellular localization assays of mutant SCRIB, protein-protein interaction assays

    PMID:22095531

    Open questions at the time
    • Limited patient cohort; causal proof in human genetics incomplete
    • Whether the trafficking defect is due to misfolding or disruption of a specific membrane-targeting signal
  7. 2013 High

    Biochemical reconstitution of the SCRIB-MRAS-SHOC2-PP1 complex revealed how SCRIB suppresses ERK signaling: SCRIB competes for PP1 within this complex, preventing SHOC2-mediated RAF dephosphorylation and thus dampening MAPK pathway output.

    Evidence Co-IP/MS, in vitro phosphatase and RAF dephosphorylation assays, dominant-negative constructs

    PMID:24211266

    Open questions at the time
    • How SCRIB is recruited to the MRAS-SHOC2 complex
    • Whether this mechanism operates at specific subcellular locations
  8. 2013 High

    Discovery that SCRIB protects integrin α5 from Rab7a-mediated lysosomal degradation showed that SCRIB controls surface receptor levels by regulating intracellular trafficking, extending its scaffold function beyond signaling to membrane protein recycling.

    Evidence Co-IP/MS, GST pulldown, TIRF microscopy, domain rescue, zebrafish morpholino knockdown

    PMID:23362312

    Open questions at the time
    • Whether SCRIB regulates recycling of other integrins or surface receptors
    • The structural basis of SCRIB-Rab7a competition
  9. 2020 High

    Mechanistic dissection in Drosophila follicle epithelium resolved that Scrib cortical recruitment depends on Dlg (not palmitoylation or phospholipids) and that Scrib-Dlg restrict aPKC indirectly by enabling Lgl activity, rather than forming a tripartite Scrib-Dlg-Lgl complex.

    Evidence Drosophila genetics, FRAP, optogenetic PIP2 depletion, light-induced oligomerization assays

    PMID:32414916

    Open questions at the time
    • Whether Dlg-dependent recruitment applies in mammalian epithelia
    • The molecular interface between Scrib and Dlg
  10. 2022 Medium

    Identification of the SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex revealed a direct role for SCRIB in membrane localization of amino acid transporters, linking polarity scaffold function to metabolic adaptation and tamoxifen resistance in breast cancer.

    Evidence Co-IP, domain mapping, siRNA knockdown, proliferation and tamoxifen resistance assays

    PMID:35501367

    Open questions at the time
    • Whether SCRIB scaffolds other transporter complexes
    • Structural basis of SCRIB N-terminal interaction with SLC3A2
  11. 2023 High

    Discovery of an evolutionarily conserved SHROOM-binding site in SCRIB's C-terminal domain established SCRIB as a direct scaffold for the SHROOM-ROCK1 contractility module, explaining how SCRIB controls apical cell shape and myosin light chain activity during gut epithelial differentiation.

    Evidence SCRIB KO in gut organ-on-chip model, domain mapping of SHROOM binding site, Co-IP, myosin localization

    PMID:37930352

    Open questions at the time
    • Whether the SHROOM-binding site is required for SCRIB function in other tissues
    • How SCRIB integrates SHROOM-ROCK1 scaffolding with its βPIX-PAK and MRAS-SHOC2 complexes
  12. 2023 Medium

    Identification of a truncated SCRIB-S isoform (lacking exon 16) that has reduced PP1 affinity and promotes ERK activation and metastasis revealed that alternative splicing of SCRIB can switch it from a tumor suppressor to a prometastatic factor.

    Evidence CLIP, RIP, splicing reporter, Co-IP for PPP1CA, ERK activity assay, ASO rescue, metastasis assay

    PMID:37402999

    Open questions at the time
    • Prevalence and regulation of SCRIB-S isoform across cancer types
    • Whether SCRIB-S retains other scaffold functions
  13. 2026 Medium

    Proximity proteomics identified SCRIB as a VE-cadherin-proximal protein that maintains adherens junction stability by organizing cortical actomyosin clusters through myosin-1c, independent of canonical catenin-actin coupling, revealing a new mechanism for junction maintenance.

    Evidence VE-cadherin proximity ligation MS, 3D angiogenesis-on-chip, siRNA KD, live imaging

    PMID:42043432

    Open questions at the time
    • Whether myosin-1c directly binds SCRIB or is recruited indirectly
    • Whether this mechanism operates in epithelia beyond endothelium

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include: how SCRIB integrates its multiple distinct scaffold complexes (βPIX-PAK, MRAS-SHOC2-PP1, SHROOM-ROCK1, SLC3A2-LLGL2) at the same membrane domain; whether complex assembly is regulated by post-translational modifications; and whether SCRIB's diverse functions are separable via domain-specific mutations in vivo.
  • No structural model of full-length SCRIB
  • Mechanism of SCRIB targeting to distinct membrane subdomains in polarized cells
  • Whether simultaneous engagement of multiple complexes occurs or is mutually exclusive

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3
Partners
ARHGEF7GIT1MRASNOS1APPAK2SHOC2SHROOM2SLC3A2
Complex memberships
SCRIB-MRAS-SHOC2-PP1SCRIB-SHROOM-ROCK1SCRIB-SLC3A2-LLGL2-SLC7A5SCRIB-βPIX-GIT-PAK

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human SCRIB (hScrib) is directly targeted for ubiquitin-mediated degradation by the high-risk HPV E6 oncoprotein in complex with the E6AP ubiquitin-protein ligase; binding is mediated by the PDZ domains of hScrib and a C-terminal PDZ-binding motif on E6. E6 expression also disrupts tight junction integrity (ZO-1 localization), dependent on the PDZ-binding epitope of E6. In vitro ubiquitination assay, in vivo degradation assay, Co-IP characterization of E6AP-E6-hScrib complex, GFP-hScrib localization in MDCK cells, ZO-1 immunofluorescence Molecular and cellular biology High 11027293
2003 Mammalian Scrb1 (Scrib) functions in the planar cell polarity (PCP) pathway; mutation in Scrb1 causes defects in stereociliary bundle polarization in mouse cochlea, and Scrb1 heterozygosity genetically interacts with Vangl2 heterozygosity to produce additive PCP defects comparable to Vangl2 homozygotes. Mouse genetics (ENU mutant), genetic epistasis (double heterozygotes), scanning electron microscopy of hair cell bundle orientation Nature High 12724779
2003 Scrib1 is required for initiation of neural tube closure; the circletail mouse harbors a frameshift mutation in Scrb1 (single base insertion causing premature termination), leading to craniorachischisis, and circletail genetically interacts with the loop-tail (Vangl2) mutant. Positional cloning, sequencing, genetic interaction (double heterozygote crosses), in situ hybridization for expression pattern Human molecular genetics High 12499390
2003 Drosophila Scrib (with Dlg and Lgl) regulates neuroblast asymmetric cell division: Scrib/Dlg/Lgl show apical cortical enrichment at prophase/metaphase, and loss-of-function mutants display defects in basal protein targeting, reduced apical cortical domain, reduced apical spindle size, and symmetric or inverted cell divisions. Drosophila genetics (loss-of-function mutants), immunofluorescence, time-lapse imaging of neuroblast divisions Nature cell biology High 12545176
2005 The tumor suppressor Scrib interacts with the zyxin-family protein LPP through Scrib's PDZ domains binding the C-terminus of LPP; both proteins co-localize at cell-cell contacts. All four PDZ domains of Scrib are dispensable for its localization to cell-cell contacts. Co-IP, pulldown assay, immunofluorescence co-localization in MDCKII and CV-1 cells BMC cell biology Medium 15649318
2005 Scrib also interacts with TRIP6 (but not zyxin, ajuba, or LIMD1) among zyxin-family proteins; TRIP6 directly binds the third PDZ domain of Scrib via its C-terminus. Both proteins localize at cell-cell contacts but are not required to target each other to these structures. PDZ domain binding assays, pulldown, immunofluorescence FEBS letters Medium 16137684
2006 Mammalian Scrib controls Cdc42 localization and activation during astrocyte polarized migration by interacting with and recruiting βPIX (a GEF for Rac/Cdc42) to the leading edge; perturbation of Scrib localization or Scrib-βPIX interaction inhibits βPIX polarized recruitment and Cdc42 activation, thereby blocking APC and Dlg1 recruitment to the leading edge. siRNA knockdown, dominant-negative constructs, Co-IP, immunofluorescence, Cdc42 activity assay (GLISA/pull-down), scratch-induced polarization assay in astrocytes Current biology : CB High 17081755
2008 Scrib is part of a protein complex containing βPIX and GIT1 that associates with PAK kinase; the Scrib complex is required for cortical PAK localization and activation by Rac at the leading edge, and for polarized Rac activation during cell migration. Loss of Scrib reduces cortical PAK and impairs chemoattractant-induced directed migration of epithelial cells and MEFs. siRNA knockdown in T47D and primary MEFs, Co-IP, immunofluorescence, PAK and Rac activity assays, chemotaxis assay Human molecular genetics High 18716323
2009 Scrib interacts with MCC (Mutated in Colorectal Cancer) in a PDZ-dependent manner; MCC also interacts with NHERF1/NHERF2/Ezrin. Reduced MCC expression impairs directed cell migration independently of Rac1, Cdc42, and PAK activation, identifying MCC as a scaffold linking Scrib to cell movement. Co-IP, siRNA knockdown, cell migration assay, immunofluorescence FEBS letters Medium 19555689
2011 Scrib negatively regulates the MAPK cascade to suppress prostate tumorigenesis; Scrib heterozygosity initiates prostate hyperplasia and biallelic loss leads to prostate intraepithelial neoplasia in mice. Loss of Scrib combined with oncogenic Kras promotes prostate cancer progression. Conditional knockout mouse model (Cre-lox), tumor histopathology, MAPK signaling assays, genetic epistasis with KrasG12D The Journal of clinical investigation High 21965329
2011 SCRIB missense variants found in human craniorachischisis patients cause loss of protein trafficking to the plasma membrane, while not affecting protein-protein interactions, implicating defective membrane localization as a pathogenic mechanism for SCRIB in neural tube defects. Sequencing, subcellular localization assay (transfection + immunofluorescence), protein-protein interaction assays Human mutation Medium 22095531
2011 SCRIB forms at least two distinct protein complexes in breast cancer cells: (1) SCRIB-ARHGEF7(βPIX)-GIT-PAK, and (2) SCRIB-NOS1AP-VANGL1. The SCRIB-NOS1AP complex colocalizes at cellular protrusions in metastatic breast cancer cells; knockdown of either NOS1AP or SCRIB reduces directed migration and prevents leading-trailing polarity establishment. Mass spectrometry, confocal microscopy, shRNA knockdown, migration assay, xenograft assay Oncogene Medium 22179838
2012 Scrib targets βPIX and PAK2 to adherens junctions where a βPIX-PAK2 complex counterbalances apoptotic stimuli transduced by Scrib itself and elicited by cadherin-mediated adhesion; the Scrib-βPIX-PAK2 complex also regulates anoikis and osmotic stress-induced apoptosis in polarized epithelia. Co-IP, shRNA knockdown, apoptosis assays, cell survival assays, osmotic stress assay, suspension culture anoikis assay Current biology : CB Medium 22863318
2012 Scrib associates with the co-chaperone Sgt1 through its leucine-rich repeat (LRR) domain; this interaction, together with HSP90, is required for Scrib protein stability. Sgt1-HSP90-mediated stabilization of Scrib is necessary for maintaining levels of the Scrib-βPix-PAK complex and for HGF-induced epithelial morphogenesis and tubulogenesis in 3D culture. Co-IP, domain mapping (LRR pulldown), HSP90 inhibitor treatment, siRNA knockdown, 3D Matrigel morphogenesis assay Journal of cell science Medium 22623728
2013 SCRIB forms a complex with MRAS and SHOC2; SCRIB functions as a PP1-regulatory protein within this complex and antagonizes SHOC2-mediated RAF dephosphorylation by competing for PP1 molecules in the same macromolecular complex, thereby negatively modulating ERK-MAPK pathway activation. Co-IP, MS, in vitro phosphatase assay, RAF dephosphorylation assay, dominant-negative constructs, tumor cell functional assays Molecular cell High 24211266
2013 Scrib interacts with integrin α5 (identified by Co-IP/MS and GST pulldown) and colocalizes with it at the basal plasma membrane of endothelial cells. Scrib supports integrin α5 recycling and protein stability by blocking its interaction with Rab7a, preventing lysosomal translocation and degradation; PDZ and LRR domains of Scrib are both required for this function. Loss of Scrib impairs directed but not random migration and delays intersegmental vessel angiogenesis in zebrafish. Co-IP/MS, GST pulldown, TIRF microscopy, siRNA knockdown, Western blot, FACS, zebrafish morpholino knockdown, domain-rescue experiments Circulation research High 23362312
2013 Loss of Scrib in mouse lens and corneal epithelium leads to EMT: E-cadherin and ZO-1 are downregulated, αSMA is upregulated, and Smad3/Smad4 accumulate in the nucleus with upregulation of Snail, indicating TGFβ signaling as a mediator of Scrib-loss-induced EMT. Conditional Scrib knockout (Cre-lox in head ectoderm), immunofluorescence, Western blot Developmental biology Medium 24095903
2013 Lpp interacts with the PCP protein Scrib in zebrafish and cooperates with Scrib for convergence and extension movements during gastrulation; knockdown of scrib causes defects in C&E movements phenocopying noncanonical Wnt signaling mutants. Morpholino knockdown in zebrafish, time-lapse analysis, Co-IP in zebrafish Developmental biology Medium 18582857
2014 Scrib interacts physically with Rac1 (but not with Vangl2) in embryonic cardiomyocytes; conditional deletion of Scrib in cardiac precursors (Nkx2.5-Cre) disrupts ventricular trabecular cytoarchitecture and causes septal defects. Genetic interaction between Scrib and Rac1 produces ventricular abnormalities, identifying a Scrib-Rac1 pathway in myocardial development. Co-IP, conditional KO mouse, histopathology, genetic epistasis (Scrib/Rac1 double mutant) Cardiovascular research Medium 25139745
2015 Scrib is asymmetrically distributed in dividing satellite (muscle stem) cells, with high Scrib in committed daughters and low Scrib in proliferating/self-renewing cells; satellite-cell-specific Scrib KO in mice causes a severe defect in muscle regeneration, demonstrating Scrib controls muscle stem cell fate and population dynamics. Conditional KO mouse (satellite-cell-specific Cre), immunofluorescence for asymmetric distribution, muscle injury/regeneration assay Cell reports High 25704816
2015 In skin carcinogenesis, apoptosis is identified as a critical effector of Scrib's tumor suppressor activity; conditional epidermal Scrib loss significantly enhances tumor multiplicity and progression in an autochthonous carcinogenesis model, and Scrib is also required for epidermal permeability barrier formation during embryogenesis. Conditional KO mouse (epidermis-specific Cre-lox), autochthonous skin carcinogenesis model, apoptosis assays, permeability assays Molecular cancer Medium 26376988
2016 Sema4A functions as a receptor in reverse signaling: Plexin-B1 binding to Sema4A promotes interaction of Sema4A with Scrib, thereby displacing Scrib from its βPIX complex and decreasing Rac1 and Cdc42 activity, which regulates cancer cell and dendritic cell migration. MS interactome screen, siRNA screening, Co-IP, Rac1/Cdc42 activity assays, cell migration assay The Journal of cell biology Medium 28007914
2017 Scrib simultaneously regulates MAPK/ERK and Hippo (Yap1) signaling pathways to suppress hepatocellular carcinoma; Scrib overexpression disrupts a positive feedback loop between Yap1 and c-Myc, reducing cyclin D1 expression. Scrib deficiency enhances liver tumor growth in vivo. Overexpression and KD in HCC cells, in vivo liver tumor model, Western blot for pathway components Oncotarget Medium 28460446
2019 SCRIB associates with the β-catenin destruction complex (identified by proteomic approach under proteasome inhibition); SCRIB/β-catenin interaction is potentiated upon Wnt3a stimulation and SCRIB plays a repressive role on Wnt/β-catenin signaling. Proteomics/MS, Co-IP, Wnt3a stimulation, transcriptional reporter assay Proteomics Medium 31513346
2019 Scrib interacts with Arhgef7 (βPix) in primary carotid endothelial cells (identified by Co-IP/MS); loss of Scrib reduces endothelial barrier function, impairs AKT phosphorylation and endothelium-dependent relaxation, and increases vascular permeability and leukocyte extravasation. Scrib also maintains expression of GATA-like protein-1 at the protein level to support VCAM-1-dependent inflammatory signaling. Conditional endothelial KO mouse, Co-IP/MS, Co-IP for GATA-like protein-1, atherosclerosis model, vascular permeability assay, siRNA Cardiovascular research Medium 30949676
2020 In Drosophila follicle epithelium, Scrib cortical recruitment requires an independent cortically stabilizing activity of Dlg rather than palmitoylation or polar phospholipid binding. Scrib and Dlg do not directly antagonize aPKC but restrict aPKC localization by enabling Lgl's aPKC-inhibiting activity. Lgl is not part of the Scrib-Dlg complex and they act in parallel. Drosophila genetics (loss-of-function mutants, rescue constructs), FRAP, optogenetic PIP2 depletion, light-induced oligomerization of basolateral proteins Proceedings of the National Academy of Sciences of the United States of America High 32414916
2020 FAM83H, SCRIB, and β-catenin form a protein complex (identified by Co-IP); knockdown of either FAM83H or SCRIB accelerates proteasomal degradation of β-catenin, indicating that the complex stabilizes β-catenin in gastric cancer cells. Co-IP, siRNA knockdown, proteasome inhibition, Western blot Aging Medium 32564009
2021 SCRIB regulates expression of sodium/iodide symporter (NIS) at the basolateral plasma membrane through a PDZ-PDZ interaction; SCRIB PDZ domains bind the C-terminal PDZ-binding motif of NIS. In CRISPR/Cas9 SCRIB-deficient cells, NIS is mislocalized to intracellular vesicular compartments, reducing iodide transport. PDZ domain array, Co-IP, CRISPR/Cas9 KO, immunofluorescence, iodide uptake assay FASEB journal High 34196428
2022 SCRIB interacts with SLC3A2 via its N-terminus to form a SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the leucine amino acid transporter. Both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ breast cancer cells; SCRIB expression is induced by estrogen in a MYC-dependent manner. Co-IP, domain mapping, siRNA knockdown, proliferation assay, tamoxifen resistance assay Communications biology Medium 35501367
2023 SCRIB controls apical cell shape and basoapical polarization of myosin light chain localization and activity during gut epithelial differentiation. SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 through an evolutionarily conserved SHROOM-binding site in the SCRIB C-terminal domain, which is required for controlling apical contractility. SCRIB KO (organ-on-chip gut model), domain mapping of SHROOM binding site, immunofluorescence for myosin localization, Co-IP The Journal of cell biology High 37930352
2023 A truncated SCRIB isoform (SCRIB-S, lacking exon 16) promotes breast cancer metastasis via ERK pathway activation; SCRIB-S has lower affinity for the phosphatase PPP1CA compared to full-length SCRIB-L. hnRNP A1 promotes exon 16 skipping by binding an 'AG'-rich sequence on intron 15 of SCRIB pre-mRNA. CLIP, RIP, MS2-GFP-based splicing assay, Co-IP for PPP1CA, ERK activity assay, antisense oligonucleotide (ASO) rescue, metastasis assay Acta pharmacologica Sinica Medium 37402999
2023 OTULIN (a linear ubiquitin deubiquitinase) interacts with SCRIB in HEK293 cells; linear (Met1-linked) ubiquitin chains associate with VANGL2 and PRICKLE1 (but not SCRIB) and direct VANGL2 surface presentation. OTULIN loss impairs VANGL2 trafficking and Wnt5a-induced filopodia extension. HEK293 interactomic analysis (BioID/MS), Co-IP, immunofluorescence, filopodia assay, VANGL2-GFP trafficking assay Disease models & mechanisms Medium 37589075
2026 Scrib controls the formation of cortical actomyosin clusters to maintain adherens junction stability and angiogenic sprouting; Scrib-depleted microvessels show adherens junction instability and decreased junctional cortex actomyosin. Myosin-1c is identified as a critical effector linking Scrib cortical dynamics to VE-cadherin stabilization, through a mechanism independent of catenin-dependent actin coupling. VE-cadherin proximity ligation mass spectrometry, 3D angiogenesis-on-chip, siRNA KD, live imaging, immunofluorescence The Journal of cell biology Medium 42043432

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 580 12724779
2000 Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase. Molecular and cellular biology 383 11027293
2003 Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Human molecular genetics 249 12499390
2003 Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nature cell biology 210 12545176
2006 Scrib controls Cdc42 localization and activity to promote cell polarization during astrocyte migration. Current biology : CB 178 17081755
2011 Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. Human mutation 156 22095531
2011 SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. The Journal of clinical investigation 147 21965329
2006 Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression. International journal of cancer 121 16619250
2011 A protein complex of SCRIB, NOS1AP and VANGL1 regulates cell polarity and migration, and is associated with breast cancer progression. Oncogene 101 22179838
2013 An MRAS, SHOC2, and SCRIB complex coordinates ERK pathway activation with polarity and tumorigenic growth. Molecular cell 95 24211266
2008 Scrib regulates PAK activity during the cell migration process. Human molecular genetics 84 18716323
2013 SCRIB and PUF60 are primary drivers of the multisystemic phenotypes of the 8q24.3 copy-number variant. American journal of human genetics 78 24140112
2013 Mutations in planar cell polarity gene SCRIB are associated with spina bifida. PloS one 63 23922697
2005 The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus. BMC cell biology 58 15649318
2013 Scrib heterozygosity predisposes to lung cancer and cooperates with KRas hyperactivation to accelerate lung cancer progression in vivo. Oncogene 50 24276238
2015 Muscle stem cell fate is controlled by the cell-polarity protein Scrib. Cell reports 48 25704816
2013 The polarity protein Scrib is essential for directed endothelial cell migration. Circulation research 45 23362312
2013 Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse. Developmental biology 37 24095903
2005 The tumor suppressor Scrib selectively interacts with specific members of the zyxin family of proteins. FEBS letters 33 16137684
2016 A reverse signaling pathway downstream of Sema4A controls cell migration via Scrib. The Journal of cell biology 32 28007914
2015 The polarity protein Scrib mediates epidermal development and exerts a tumor suppressive function during skin carcinogenesis. Molecular cancer 32 26376988
2021 SCRIB Promotes Proliferation and Metastasis by Targeting Hippo/YAP Signalling in Colorectal Cancer. Frontiers in cell and developmental biology 30 33937255
2017 The cell polarity protein Scrib functions as a tumor suppressor in liver cancer. Oncotarget 29 28460446
2020 Distinct activities of Scrib module proteins organize epithelial polarity. Proceedings of the National Academy of Sciences of the United States of America 27 32414916
2012 A βPIX-PAK2 complex confers protection against Scrib-dependent and cadherin-mediated apoptosis. Current biology : CB 26 22863318
2010 Tumor suppressors Sav/Scrib and oncogene Ras regulate stem-cell transformation in adult Drosophila malpighian tubules. Journal of cellular physiology 26 20432470
2009 MCC, a new interacting protein for Scrib, is required for cell migration in epithelial cells. FEBS letters 26 19555689
2014 Scrib:Rac1 interactions are required for the morphogenesis of the ventricular myocardium. Cardiovascular research 23 25139745
2008 Lpp is involved in Wnt/PCP signaling and acts together with Scrib to mediate convergence and extension movements during zebrafish gastrulation. Developmental biology 22 18582857
2024 Cycloastragenol reduces microglial NLRP3 inflammasome activation in Parkinson's disease models by promoting autophagy and reducing Scrib-driven ROS. Phytomedicine : international journal of phytotherapy and phytopharmacology 19 39522252
2021 Ras Tumors: A Cooperative Oncogenesis Model Fueled by Tumor/Host Interactions. International journal of molecular sciences 19 34445578
2020 FAM83H and SCRIB stabilize β-catenin and stimulate progression of gastric carcinoma. Aging 18 32564009
2018 The SCRIB Paralog LANO/LRRC1 Regulates Breast Cancer Stem Cell Fate through WNT/β-Catenin Signaling. Stem cell reports 18 30344009
2009 CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without affecting cell polarity. Molecular biology of the cell 18 19726564
2022 Polarity protein SCRIB interacts with SLC3A2 to regulate proliferation and tamoxifen resistance in ER+ breast cancer. Communications biology 17 35501367
2021 ZnT7 RNAi favors RafGOFscrib-/--induced tumor growth and invasion in Drosophila through JNK signaling pathway. Oncogene 16 33649534
2020 Lgl cortical dynamics are independent of binding to the Scrib-Dlg complex but require Dlg-dependent restriction of aPKC. Development (Cambridge, England) 15 32665243
2008 Differential regulation of Dlg1, Scrib, and Lgl1 expression in a transgenic mouse model of ocular cancer. Molecular vision 15 19098995
2019 The Tumor Suppressor SCRIB is a Negative Modulator of the Wnt/β-Catenin Signaling Pathway. Proteomics 14 31513346
2012 Scrib regulates HGF-mediated epithelial morphogenesis and is stabilized by Sgt1-HSP90. Journal of cell science 14 22623728
2009 Role of Scrib and Dlg in anterior-posterior patterning of the follicular epithelium during Drosophila oogenesis. BMC developmental biology 14 19948068
2022 MiR-9-5p Inhibits the MMP+-Induced Neuron Apoptosis through Regulating SCRIB/β-Catenin Signaling in Parkinson's Disease. Oxidative medicine and cellular longevity 13 35509839
2021 The PDZ protein SCRIB regulates sodium/iodide symporter (NIS) expression at the basolateral plasma membrane. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 11 34196428
2019 The polarity protein Scrib limits atherosclerosis development in mice. Cardiovascular research 11 30949676
2018 scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin mediated mitochondrial dynamics in the wing imaginal tissues of Drosophila. Mitochondrion 11 29360576
2014 Xihuang Pill () induces mesenchymal-epithelial transition and inhibits loss of apical-basal polarity in colorectal cancer cell through regulating ZEB1-SCRIB loop. Chinese journal of integrative medicine 10 24802235
2023 Truncated SCRIB isoform promotes breast cancer metastasis through HNRNP A1 mediated exon 16 skipping. Acta pharmacologica Sinica 9 37402999
2020 Low SCRIB expression in fibroblasts promotes invasion of lung cancer cells. Life sciences 9 32534038
2021 SCRIB Is Involved in the Progression of Ovarian Carcinomas in Association with the Factors Linked to Epithelial-to-Mesenchymal Transition and Predicts Shorter Survival of Diagnosed Patients. Biomolecules 8 33803371
2015 Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling. Arteriosclerosis, thrombosis, and vascular biology 8 26205961
2022 MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells. Journal of dental research 7 35259994
2022 PDZ Proteins SCRIB and DLG1 Regulate Myeloma Cell Surface CD86 Expression, Growth, and Survival. Molecular cancer research : MCR 7 35380688
2023 SCRIB controls apical contractility during epithelial differentiation. The Journal of cell biology 6 37930352
2021 Human DLG1 and SCRIB Are Distinctly Regulated Independently of HPV-16 during the Progression of Oropharyngeal Squamous Cell Carcinomas: A Preliminary Analysis. Cancers 6 34503271
2018 PUF60-SCRIB fusion transcript in a patient with 8q24.3 microdeletion and atypical Verheij syndrome. European journal of medical genetics 6 30472487
2016 Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival. EBioMedicine 6 27428426
2013 The internal structure of embryonic gonads and testis development in Drosophila melanogaster requires scrib, lgl and dlg activity in the soma. The International journal of developmental biology 6 23585349
2022 Neuron-Specific Deletion of Scrib in Mice Leads to Neuroanatomical and Locomotor Deficits. Frontiers in genetics 5 35692812
2020 Scrib and Dlg1 polarity proteins regulate Ag presentation in human dendritic cells. Journal of leukocyte biology 5 32293058
2022 Individual and Co-Expression Patterns of FAM83H and SCRIB at Diagnosis Are Associated with the Survival of Colorectal Carcinoma Patients. Diagnostics (Basel, Switzerland) 4 35885485
2021 Scrib module proteins: Control of epithelial architecture and planar spindle orientation. The international journal of biochemistry & cell biology 4 33962021
2018 Diverging impact of cell fate determinants Scrib and Llgl1 on adhesion and migration of hematopoietic stem cells. Journal of cancer research and clinical oncology 2 30083817
2013 Molecular Expression of the Scribble Complex Genes, Dlg, Scrib and Lgl, in Silkworm, Bombyx mori. Genes 2 24705163
2010 No association of polymorphisms in the cell polarity gene SCRIB with breast cancer risk. Breast cancer research and treatment 2 20936341
2023 An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity. Disease models & mechanisms 1 37589075
2026 Potential anticancer activity of Shulva Yoga, a herbo-metallic compound, in loss of scrib induced cancer in Drosophila melanogaster. Journal of Ayurveda and integrative medicine 0 41690165
2026 Scrib organizes cortical actomyosin clusters to maintain adherens junctions and angiogenic sprouting. The Journal of cell biology 0 42043432
2022 Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques. Molecular diversity 0 35648249
2008 [Scrib, a tumor suppressor gene involved in cell polarity]. Medecine sciences : M/S 0 18198112