Affinage

SCRIB

SCRIB overlapping open reading frame protein · UniProt C0HLS1

Length
120 aa
Mass
12.0 kDa
Annotated
2026-06-10
69 papers in source corpus 37 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SCRIB is a leucine-rich-repeat and PDZ-domain scaffold protein that organizes polarity- and migration-controlling signaling complexes at the basolateral membrane and cell-cell junctions of polarized epithelia and endothelia (PMID:17081755, PMID:23362312). It functions as a core planar cell polarity (PCP) gene, acting in the same pathway as VANGL2 to control neural tube closure and cochlear hair-cell stereociliary polarization, with PCP-associated human missense variants disrupting SCRIB trafficking to the plasma membrane (PMID:12724779, PMID:12499390, PMID:22095531). A central mechanistic theme is its recruitment of the βPIX(ARHGEF7)/GIT/PAK module to the leading edge and to adherens junctions, where it controls polarized Cdc42 and Rac1 activation during directed migration and modulates anoikis (PMID:17081755, PMID:18716323, PMID:22863318); Semaphorin-4A/Plexin-B1 reverse signaling antagonizes migration by stripping SCRIB from this βPIX complex (PMID:28007914). SCRIB also acts as a tumor suppressor that restrains the RAS-MAPK/ERK pathway — it serves as a PP1-regulatory protein within an MRAS-SHOC2-SCRIB complex, competing for PP1 to antagonize SHOC2-mediated RAF activation — and its loss synergizes with oncogenic KRAS to drive tumorigenesis (PMID:24211266, PMID:21965329, PMID:24276238). Through PDZ- and LRR-mediated cargo retention it stabilizes membrane proteins including integrin α5, the sodium/iodide symporter NIS, and the SLC7A5/SLC3A2 amino acid transporter, preventing their lysosomal degradation or mislocalization (PMID:23362312, PMID:34196428, PMID:35501367). At junctions SCRIB organizes cortical actomyosin via VE-cadherin and myosin-1c and scaffolds SHROOM2/4-ROCK1 to control apical contractility (PMID:42043432, PMID:37930352), and it additionally represses Wnt/β-catenin, Hippo/YAP, and TGFβ/Smad-driven EMT signaling (PMID:31513346, PMID:28460446, PMID:24095903). SCRIB protein stability is maintained by the Sgt1-HSP90 chaperone system acting on its LRR domain, and it is targeted for E6AP-dependent ubiquitin-mediated degradation by high-risk HPV E6 proteins (PMID:22623728, PMID:11027293).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2000 High

    Established that human Scrib is a direct target of viral oncoprotein-driven degradation, linking it to epithelial junction integrity and the first mechanistic handle on its destruction.

    Evidence In vitro ubiquitination, Co-IP, and E6 expression with ZO-1 immunofluorescence in MDCK cells

    PMID:11027293

    Open questions at the time
    • Did not define SCRIB's normal cellular function beyond junction maintenance
    • Endogenous (non-viral) ubiquitin ligase for SCRIB not identified
  2. 2003 High

    Genetic epistasis in mouse and Drosophila placed Scrib in the planar cell polarity pathway with Vangl2 and revealed its role in asymmetric division and neural tube closure, defining it as a polarity gene rather than only an HPV target.

    Evidence Mouse Scrb1 × Vangl2 double heterozygotes, circletail positional cloning, and Drosophila scrib loss-of-function neuroblast analysis

    PMID:12499390 PMID:12545176 PMID:12724779

    Open questions at the time
    • Molecular mechanism connecting Scrib to Vangl2 not resolved
    • Whether interaction with Vangl2 is direct was not established
  3. 2006 High

    Identified the βPIX/GIT/PAK module as the effector complex through which SCRIB controls polarized Cdc42/Rac1 activation, providing the molecular mechanism for SCRIB's role in directed migration.

    Evidence siRNA, dominant-negative constructs, GTPase activity assays, and scratch-wound migration in astrocytes; reciprocal Co-IP in T47D cells and MEFs

    PMID:17081755 PMID:18716323

    Open questions at the time
    • Stoichiometry and assembly hierarchy of the SCRIB-βPIX-GIT-PAK complex not defined
    • How SCRIB itself is polarized to the leading edge unresolved
  4. 2011 Medium

    In vivo knockout models defined SCRIB as a tumor suppressor that restrains MAPK output, and proteomics resolved it into distinct βPIX-PAK and VANGL-NOS1AP complexes, separating its signaling and polarity functions.

    Evidence Conditional/constitutive Scrib KO mouse prostate models with MAPK western blots; mass spectrometry and shRNA in metastatic breast cancer cells

    PMID:21965329 PMID:22179838

    Open questions at the time
    • Direct biochemical mechanism by which SCRIB suppresses MAPK not yet established in 2011
    • Functional separation of the two complexes incompletely mapped
  5. 2013 High

    Biochemical reconstitution revealed how SCRIB suppresses ERK signaling — as a PP1-regulatory protein in the MRAS-SHOC2 complex that competes for PP1 to block RAF dephosphorylation — and KRAS-cooperation models confirmed the tumor-suppressor mechanism in vivo.

    Evidence Co-IP, phosphatase and competition assays, RAF/ERK phospho-westerns; LSL-KRas(G12D);Scrib mouse lung cancer model

    PMID:24211266 PMID:24276238

    Open questions at the time
    • Quantitative PP1 partitioning between SCRIB and SHOC2 in cells not measured
    • Cell-context dependence of the competition mechanism unresolved
  6. 2013 High

    Demonstrated SCRIB acts as a cargo-retention scaffold, stabilizing integrin α5 at the basal membrane by preventing Rab7a-dependent lysosomal degradation, extending its role from signaling to membrane protein homeostasis.

    Evidence Co-IP/MS, GST pulldown, TIRF, FACS, lysosome trafficking assays, and domain-mutant rescue

    PMID:23362312

    Open questions at the time
    • Whether retention is direct PDZ binding or via an adaptor not fully resolved
    • Generality of the lysosomal-rescue mechanism to other cargo not yet tested in this study
  7. 2013 Medium

    Linked SCRIB loss to TGFβ/Smad-driven EMT and to vertebrate convergence-extension, broadening its tumor-suppressor and PCP roles to defined transcriptional and morphogenetic outputs.

    Evidence Conditional Scrib deletion in mouse lens/cornea with EMT marker and nuclear Smad analysis; zebrafish scrib morpholino with Lpp Co-IP

    PMID:18582857 PMID:24095903

    Open questions at the time
    • Direct molecular link between SCRIB and Smad regulation not defined
    • Whether EMT suppression is cell-autonomous unresolved
  8. 2015 High

    Established SCRIB control of stem-cell fate and apoptosis-dependent tumor suppression, showing asymmetric SCRIB partitioning instructs muscle stem cell differentiation and that apoptosis is the critical effector of its skin tumor-suppressor activity.

    Evidence Satellite-cell-specific and epidermal conditional Scrib KO mice with regeneration and DMBA/TPA carcinogenesis assays

    PMID:25704816 PMID:26376988

    Open questions at the time
    • Mechanism establishing asymmetric SCRIB inheritance unknown
    • Molecular pathway connecting SCRIB to apoptosis regulation not defined
  9. 2020 High

    Rigorous biophysical dissection in Drosophila redefined Scrib module assembly, showing Lgl is not a stable Scrib-Dlg complex member and that Scrib/Dlg restrict aPKC indirectly by enabling Lgl activity.

    Evidence FRAP, optogenetic oligomerization and PIP2 depletion, and epistatic genetics in follicle epithelium

    PMID:32414916 PMID:32665243

    Open questions at the time
    • Mammalian generality of this Lgl-independent assembly not tested
    • The cortical stabilizing activity of Dlg molecularly undefined
  10. 2021 High

    Confirmed PDZ-dependent cargo retention as a recurring SCRIB mechanism, showing it holds the iodide symporter NIS and the SLC7A5/SLC3A2 transporter at the membrane, with proliferation and drug-resistance consequences.

    Evidence PDZ array binding, Co-IP, CRISPR KO with iodide transport assay (NIS); domain-mapped Co-IP and proliferation/tamoxifen assays (SLC3A2)

    PMID:34196428 PMID:35501367

    Open questions at the time
    • Whether NIS and amino acid transporter retention share a common mechanism untested
    • In vivo relevance of transporter retention not established
  11. 2023 Medium

    Identified SCRIB as the scaffold for SHROOM2/4-ROCK1 apical contractility machinery and characterized a splicing-generated SCRIB-S isoform with reduced PP1 affinity that drives ERK-dependent metastasis, connecting isoform choice to signaling output.

    Evidence Organ-on-chip SCRIB KO with myosin light chain analysis and domain mutagenesis; CLIP/RIP, PPP1CA affinity pulldown, and metastasis assays for SCRIB-S

    PMID:37402999 PMID:37930352

    Open questions at the time
    • Regulation of SCRIB splice-isoform ratio in normal tissue unclear
    • Structural basis of SHROOM-binding-site engagement of ROCK1 not resolved
  12. 2026 High

    Resolved a junction-stabilizing mechanism in endothelium, showing SCRIB binds VE-cadherin and uses myosin-1c to organize cortical actomyosin independently of catenin-mediated cadherin-actin coupling during angiogenesis.

    Evidence VE-cadherin proximity ligation mass spectrometry, 3D angiogenesis-on-chip, TIRF, Co-IP, and siRNA

    PMID:42043432

    Open questions at the time
    • Whether myosin-1c effector role generalizes to epithelial junctions untested
    • Direct vs adaptor-mediated SCRIB-VE-cadherin binding not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SCRIB selects among its many parallel functions — PCP, βPIX/Rac signaling, ERK suppression, cargo retention, junction actomyosin, and Wnt/Hippo/TGFβ regulation — within a single polarized cell, and what spatiotemporal cues partition its scaffold pool, remains unresolved.
  • No integrated model of how distinct SCRIB complexes are spatially or temporally segregated
  • Endogenous regulators of SCRIB localization and abundance incompletely mapped
  • Structural basis of multi-complex assembly on the LRR/PDZ scaffold undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005886 plasma membrane 5 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-1643685 Disease 4 R-HSA-162582 Signal Transduction 3 R-HSA-9609507 Protein localization 3 R-HSA-5357801 Programmed Cell Death 2
Partners
ARHGEF7MRASPAKROCK1SHOC2SHROOM2VANGL2VE-CADHERIN
Complex memberships
MRAS-SHOC2-SCRIBSCRIB-ARHGEF7(βPIX)-GIT-PAKSCRIB-NOS1AP-VANGLSCRIB/SLC3A2/LLGL2/SLC7A5

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 Human Scrib (hScrib) is targeted for ubiquitin-mediated degradation by high-risk HPV E6 proteins in complex with the E6AP ubiquitin-protein ligase; hScrib binds directly to E6 via its PDZ domains interacting with a conserved C-terminal PDZ-binding motif on E6. E6 expression induces degradation of hScrib in vivo and loss of tight junction integrity (ZO-1 mislocalization), dependent on the PDZ-binding epitope of E6. In vitro ubiquitination assay, co-immunoprecipitation, GFP-hScrib localization in MDCK cells, E6 expression with ZO-1 immunofluorescence Molecular and cellular biology High 11027293
2003 Mutation in mouse Scrb1 causes defects in polarization of stereociliary bundles in cochlear hair cells, and Scrb1 genetically interacts with Vangl2 (Loop-tail) in regulating planar cell polarity (PCP) in mammals; double heterozygotes show phenotypes comparable to Vangl2 homozygotes, establishing Scrb1 as a PCP gene. Mouse genetics, genetic epistasis (Scrb1 × Vangl2 double heterozygotes), cochlear hair cell morphology analysis Nature High 12724779
2003 Disruption of Scrb1 in the circletail mouse (single-base insertion causing frameshift and premature stop) causes craniorachischisis; Scrb1 expression overlaps with Vangl2 expression and circletail genetically interacts with loop-tail (Vangl2), placing Scrb1 in the same pathway as Vangl2 for neural tube closure initiation. Positional cloning, sequencing, expression analysis, genetic interaction (Crc × loop-tail cross) Human molecular genetics High 12499390
2003 Drosophila Scrib (with Dlg and Lgl) regulates neuroblast asymmetric cell division: Scrib shows apical cortical enrichment at prophase/metaphase, and scrib mutants display defects in basal protein targeting, reduced apical cortical domain size, and asymmetric mitotic spindle defects leading to symmetric or inverted cell divisions. Drosophila genetics, immunofluorescence, loss-of-function mutant analysis Nature cell biology High 12545176
2005 Scrib directly interacts with the zyxin family member LPP via its PDZ domains binding to the C-terminus of LPP; both proteins colocalize at cell-cell contacts. The interaction links Scrib to a signaling pathway between cell-cell contacts and the nucleus. Co-immunoprecipitation, GST pulldown, immunofluorescence colocalization in MDCKII and CV-1 cells BMC cell biology Medium 15649318
2005 Scrib also interacts with TRIP6 (another zyxin family member) via its third PDZ domain binding to the TRIP6 C-terminus, but does not interact with zyxin, ajuba, or LIMD1, demonstrating selectivity in Scrib PDZ-domain interactions. Co-immunoprecipitation, GST pulldown with deletion constructs, immunofluorescence FEBS letters Medium 16137684
2006 Mammalian Scrib controls Cdc42 localization and activation during astrocyte polarized migration by interacting and colocalizing with βPIX (a GEF for Rac/Cdc42) at the leading edge; perturbation of Scrib localization or Scrib-βPIX interaction inhibits βPIX polarized recruitment and Cdc42 activation, which in turn impairs APC and Dlg1 recruitment to the leading edge. siRNA knockdown, dominant-negative constructs, immunofluorescence, scratch-wound migration assay, Cdc42 activity assays Current biology : CB High 17081755
2008 Scrib associates with PAK (a serine-threonine kinase) through the βPIX/GIT1 scaffold complex at the leading edge; Scrib-deficient cells show decreased cortical PAK, impaired PAK activation by Rac, and loss of polarized active Rac at the leading edge, demonstrating that Scrib is required for PAK and Rac function during cell migration. Co-immunoprecipitation, immunofluorescence, siRNA knockdown in T47D cells and primary MEFs, chemotaxis assay, active Rac immunofluorescence Human molecular genetics High 18716323
2009 Scrib interacts with MCC (a binding partner for β-catenin) in a PDZ-dependent manner; MCC and Scrib colocalize at the cell membrane, and reduced MCC expression impairs directed cell migration independently of Rac1, Cdc42, and PAK activation. Yeast two-hybrid (isolation), co-immunoprecipitation, immunofluorescence, siRNA knockdown, migration assay FEBS letters Medium 19555689
2011 Scrib negatively regulates the MAPK cascade to suppress prostate tumorigenesis; Scrib heterozygosity promotes prostate hyperplasia and biallelic Scrib loss leads to prostate intraepithelial neoplasia in mice, with elevated MAPK signaling as the mechanistic driver. Conditional/constitutive knockout mouse models, western blot (MAPK), histopathology, in vivo tumor models The Journal of clinical investigation Medium 21965329
2011 Missense variants in human SCRIB associated with craniorachischisis cause profound alteration in subcellular protein localization, with diminution or abolition of trafficking to the plasma membrane, identifying defective PCP protein trafficking as a pathogenic mechanism. Sequencing of patient samples, subcellular localization assays for variant proteins in cells Human mutation Medium 22095531
2011 SCRIB forms at least two distinct protein complexes: (1) SCRIB-ARHGEF7(βPIX)-GIT-PAK and (2) SCRIB-NOS1AP-VANGL; NOS1AP colocalizes with SCRIB and VANGL1 along cellular protrusions in metastatic breast cancer cells. Knockdown of NOS1AP or SCRIB slows breast cancer cell migration and prevents leading-trailing polarity establishment. Mass spectrometry, confocal microscopy, shRNA knockdown, migration assay Oncogene Medium 22179838
2012 Scrib targets βPIX and PAK2 to adherens junctions; a βPIX-PAK2 complex counterbalances apoptotic stimuli transduced by Scrib and elicited by cadherin-mediated cell-cell adhesion. The Scrib-βPIX-PAK2 complex at adherens junctions modulates anoikis and cell survival in response to osmotic stress. Co-immunoprecipitation, immunofluorescence at adherens junctions, siRNA knockdown, apoptosis/anoikis assays Current biology : CB Medium 22863318
2012 Scrib's leucine-rich repeat (LRR) domain associates with the co-chaperone Sgt1; HSP90 is also required for Sgt1-Scrib association, and both Sgt1 and HSP90 maintain proper Scrib protein levels. Reduced Scrib stability (following Sgt1-HSP90 inhibition) lowers the abundance of the Scrib-βPIX-PAK complex and blocks HGF-mediated epithelial morphogenesis. Co-immunoprecipitation, domain mapping, HSP90 inhibitor treatment, 3D morphogenesis assay, western blot Journal of cell science Medium 22623728
2013 SCRIB and MRAS form a complex with SHOC2; SCRIB functions as a PP1-regulatory protein within this complex and antagonizes SHOC2-mediated RAF dephosphorylation through competition for PP1 molecules, thereby suppressing ERK pathway activation. MRAS coordinates ERK pathway dynamics with polarity via this macromolecular complex. Co-immunoprecipitation, biochemical competition assay, phosphatase assays, western blot for RAF/ERK phosphorylation Molecular cell High 24211266
2013 SCRIB interacts with integrin α5 (identified by Co-IP/mass spectrometry and GST pulldown); Scrib and integrin α5 colocalize at the basal plasma membrane. Scrib depletion reduces integrin α5 protein levels and surface expression by promoting its interaction with Rab7a, lysosomal translocation, and pepstatin-sensitive protease-dependent degradation. Both PDZ and LRR domains of Scrib are required for integrin α5 rescue and directional migration. Co-IP/mass spectrometry, GST pulldown, TIRF microscopy, FACS, western blot, siRNA knockdown, lysosome trafficking assays, domain-mutant rescue Circulation research High 23362312
2013 In vivo zebrafish knockdown of scrib causes defects in convergence and extension (C&E) movements during gastrulation; Lpp interacts with Scrib (PCP protein) and cooperates with Scrib to mediate C&E, placing Scrib in the noncanonical Wnt/PCP pathway in vertebrates. Morpholino knockdown in zebrafish, co-immunoprecipitation, time-lapse analysis, genetic interaction Developmental biology Medium 18582857
2013 Scrib loss in mouse lens and corneal epithelium leads to epithelial-to-mesenchymal transition (EMT); mechanistically, Scrib deficiency causes nuclear accumulation of Smad3/Smad4 (TGFβ intermediates), upregulation of Snail, downregulation of E-cadherin and ZO-1, and upregulation of αSMA, placing Scrib as a suppressor of TGFβ-mediated EMT. Conditional Cre-loxP Scrib deletion in lens/cornea, immunofluorescence for EMT markers, western blot, nuclear Smad localization Developmental biology Medium 24095903
2013 In vivo loss of Scrib in mice (Scrib+/- and Scrib-specific KO) combined with oncogenic KRas(G12D) promotes lung cancer progression, likely through synergistic elevation of RAS-MAPK signaling, showing Scrib acts as a tumor suppressor that limits MAPK output. LSL-KRas(G12D) mouse model crossed with Scrib heterozygous mice, western blot for MAPK pathway, histopathology Oncogene Medium 24276238
2013 In zebrafish, in vivo dissection of the 8q24.3 CNV shows that SCRIB (as a planar cell polarity effector) and PUF60 (splicing factor) make discrete contributions to a multisystem syndromic phenotype, and their combined suppression exacerbates some phenotypic components, demonstrating a binary genetic interaction. Zebrafish morpholino knockdown, combinatorial suppression, phenotypic rescue American journal of human genetics Medium 24140112
2014 Scrib interacts physically with Rac1 in embryonic cardiomyocytes (but not with Vangl2 in this tissue); genetic interaction between Scrib and Rac1 is required for proper cytoarchitecture of ventricular trabeculae. Cardiac-specific deletion of Scrib (Nkx2.5-Cre) causes trabecular disruption, ventricular septal defects, and cardiac fibrosis. Conditional Cre-loxP KO, co-immunoprecipitation for Scrib-Rac1 and Scrib-Vangl2, histopathology, cardiac morphology analysis Cardiovascular research Medium 25139745
2015 Scrib is asymmetrically distributed in dividing satellite (muscle stem) cells, with high Scrib levels in daughter cells committed to myogenic differentiation. Satellite-cell-specific Scrib KO causes a severe defect in muscle regeneration, demonstrating Scrib controls muscle stem cell fate decisions (self-renewal vs. differentiation). Conditional satellite-cell-specific Scrib KO mice, immunofluorescence for asymmetric distribution, muscle injury/regeneration assay Cell reports High 25704816
2016 Plexin-B1 binding to transmembrane Sema4A triggers reverse signaling; Scrib is a downstream effector of Sema4A identified by mass spectrometry + siRNA screening. Plexin-B1 binding to Sema4A promotes the Sema4A-Scrib interaction, thereby removing Scrib from its βPIX complex, decreasing Rac1 and Cdc42 activity and inhibiting cell migration. Mass spectrometry, siRNA screening, co-immunoprecipitation, Rac1/Cdc42 activity assays, cell migration assay The Journal of cell biology Medium 28007914
2017 Scrib overexpression in hepatocellular carcinoma cells suppresses proliferation by simultaneously regulating MAPK/ERK and Hippo signaling pathways, disrupting a positive feedback loop between Yap1 and c-Myc, and suppressing expression of Yap1, c-Myc, and cyclin D1. Scrib overexpression and knockdown in HCC cells, western blot for Yap1/c-Myc/cyclin D1/ERK/Hippo pathway, in vivo mouse liver tumor model Oncotarget Medium 28460446
2019 SCRIB associates with the β-catenin destruction complex under proteasome inhibition; the SCRIB/β-catenin interaction is potentiated upon Wnt3a stimulation; SCRIB plays a repressing role on Wnt/β-catenin signaling. Proteomic interactome (mass spectrometry), co-immunoprecipitation, Wnt reporter assay, western blot Proteomics Medium 31513346
2019 Scrib interacts with Arhgef7 (βPIX) in primary carotid endothelial cells (identified by Co-IP/MS); siRNA knockdown of Scrib or Arhgef7 reduces endothelial barrier function. Scrib KO reduces AKT phosphorylation and endothelium-dependent relaxation while increasing vascular permeability and leukocyte extravasation. Scrib also interacts with the transcription factor GATA-like protein-1 (GLP1) and maintains its protein abundance. Co-IP/mass spectrometry, siRNA knockdown, endothelial barrier function assay, conditional endothelial KO mice, western blot (AKT), in vivo atherosclerosis models Cardiovascular research Medium 30949676
2020 In Drosophila follicle epithelium, Scrib module proteins have distinct activities: cortical recruitment of Scrib requires an independent cortical stabilizing activity of Dlg (not palmitoylation or polar phospholipid binding). Scrib and Dlg do not directly antagonize aPKC but instead restrict aPKC localization by enabling Lgl's aPKC-inhibiting activity. Lgl is not part of the Scrib-Dlg complex at the lateral domain. Drosophila genetics, fluorescence recovery after photobleaching (FRAP), optogenetics, loss-of-function mutants, immunofluorescence Proceedings of the National Academy of Sciences of the United States of America High 32414916
2020 Lgl does not form immobile complexes with Scrib-Dlg at the lateral domain of Drosophila follicle cells (shown by FRAP); Dlg and Scrib are required only for Lgl localization and dynamics in the presence of aPKC function. Light-induced oligomerization confirms Lgl is not part of the Scrib-Dlg complex. FRAP, optogenetic depletion of plasma membrane PIP2, optogenetic oligomerization of basolateral proteins, genetic mutants Development (Cambridge, England) High 32665243
2021 SCRIB's PDZ domains interact with the C-terminal PDZ-binding motif of the sodium/iodide symporter (NIS), retaining NIS at the basolateral plasma membrane; CRISPR/Cas9-based SCRIB knockout causes NIS mislocalization to intracellular vesicular compartments (late endosomes/lysosomes), impairing iodide transport. PDZ domain array binding assay, co-immunoprecipitation, CRISPR/Cas9 KO cells, immunofluorescence, iodide transport assay FASEB journal High 34196428
2022 SCRIB interacts with SLC3A2 (heteromeric component of leucine amino acid transporter SLC7A5) via the N-terminus of SCRIB, facilitating formation of a SCRIB/SLC3A2/LLGL2/SLC7A5 quaternary complex required for membrane localization of the amino acid transporter; both SCRIB and SLC3A2 are required for cell proliferation and tamoxifen resistance in ER+ breast cancer cells. Co-immunoprecipitation, domain mapping, siRNA knockdown, membrane fractionation, proliferation assay, tamoxifen resistance assay Communications biology Medium 35501367
2023 SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 through an evolutionary conserved SHROOM-binding site in the SCRIB C-terminus; SCRIB KO gut epithelia show reduced apical cell shape area and impaired basoapical polarization of myosin light chain localization and activity, demonstrating SCRIB controls epithelial apical contractility during differentiation. Organ-on-chip model, SCRIB KO, immunofluorescence for myosin light chain, co-immunoprecipitation for SHROOM/ROCK1, domain mutagenesis The Journal of cell biology High 37930352
2023 hnRNP A1 promotes SCRIB exon 16 skipping by binding an 'AG'-rich sequence on intron 15 of SCRIB pre-mRNA, generating a truncated SCRIB-S isoform; SCRIB-S has lower affinity for the phosphatase subunit PPP1CA compared to full-length SCRIB-L, and promotes breast cancer metastasis through ERK pathway activation. CLIP, RIP, MS2-GFP-based RNA binding assay, affinity pulldown for PPP1CA, siRNA/antisense oligonucleotide manipulation, ERK western blot, metastasis assay Acta pharmacologica Sinica Medium 37402999
2023 OTULIN (Met1-Ub deubiquitinase) interacts with SCRIB; Met1-Ub chains associate with VANGL2 and PRICKLE1 (but not SCRIB) and can direct VANGL2 surface presentation, suggesting linear ubiquitination of PCP complex components is regulated in part through SCRIB-associated machinery. HEK293 cell interactomic analysis, co-immunoprecipitation, MDCK cell VANGL2-GFP trafficking assay, OTULIN KO mouse neural tube analysis Disease models & mechanisms Medium 37589075
2024 Scrib controls reactive oxygen species production in microglia by regulating Scrib-associated NADPH oxidase (p22phox expression); suppression of Scrib reduces ROS and NLRP3 inflammasome activation. Scrib siRNA knockdown in primary microglia, ROS measurement, western blot for p22phox and NLRP3 components Phytomedicine Low 39522252
2026 Scrib directly interacts with VE-cadherin (identified by proximity ligation mass spectrometry) and organizes cortical actomyosin clusters at endothelial cell-cell junctions; Scrib depletion decreases junctional actomyosin without affecting catenin-dependent VE-cadherin-actin coupling. Myosin-1c is identified as a critical effector linking Scrib cortical dynamics and VE-cadherin to stabilize adherens junctions during angiogenesis. VE-cadherin proximity ligation mass spectrometry, 3D angiogenesis-on-chip, siRNA knockdown, actomyosin immunofluorescence, TIRF, co-immunoprecipitation The Journal of cell biology High 42043432
2020 FAM83H, SCRIB, and β-catenin form a complex (co-immunoprecipitation); knockdown of either FAM83H or SCRIB accelerates proteasomal degradation of β-catenin, indicating SCRIB participates in stabilizing β-catenin. Co-immunoprecipitation, siRNA knockdown, western blot for β-catenin, proteasome inhibitor treatment Aging Medium 32564009
2015 Conditional biallelic loss of Scrib in mouse epidermis significantly enhances tumor multiplicity and progression in an autochthonous skin carcinogenesis model; mechanistically, apoptosis is identified as the critical effector of Scrib tumor suppressor activity during skin carcinogenesis. Cre-loxP conditional Scrib KO in epidermis, DMBA/TPA skin carcinogenesis model, apoptosis markers (immunofluorescence/western blot) Molecular cancer Medium 26376988

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 581 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 384 11027293
2003 Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Human molecular genetics 251 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 157 22095531
2011 SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. The Journal of clinical investigation 148 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 96 24211266
2008 Scrib regulates PAK activity during the cell migration process. Human molecular genetics 85 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 51 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 46 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 28 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 24 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 21 39522252
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 20 19726564
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
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) 16 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
2019 The polarity protein Scrib limits atherosclerosis development in mice. Cardiovascular research 13 30949676
2018 scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin mediated mitochondrial dynamics in the wing imaginal tissues of Drosophila. Mitochondrion 12 29360576
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
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
2015 Polarity Protein Scrib Facilitates Endothelial Inflammatory Signaling. Arteriosclerosis, thrombosis, and vascular biology 9 26205961
2022 MUC1 and Polarity Markers INADL and SCRIB Identify Salivary Ductal Cells. Journal of dental research 8 35259994
2022 PDZ Proteins SCRIB and DLG1 Regulate Myeloma Cell Surface CD86 Expression, Growth, and Survival. Molecular cancer research : MCR 8 35380688
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
2023 SCRIB controls apical contractility during epithelial differentiation. The Journal of cell biology 7 37930352
2016 Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival. EBioMedicine 7 27428426
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
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
2026 Scrib organizes cortical actomyosin clusters to maintain adherens junctions and angiogenic sprouting. The Journal of cell biology 1 42043432
2023 An interaction between OTULIN and SCRIB uncovers roles for linear ubiquitination in planar cell polarity. Disease models & mechanisms 1 37589075
2022 Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques. Molecular diversity 1 35648249
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
2008 [Scrib, a tumor suppressor gene involved in cell polarity]. Medecine sciences : M/S 0 18198112

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