Genomes and Genes
Gene Symbol: scrib
Alias: 0424/05, CG31082, CG42614, CG43398, CG5462, CG5467, CT17324, Dmel\CG43398, Dmel_CG31082, Dmel_CG42614, Dmel_CG5462, Dmel_CG5467, MENE (3R)-F, SCR, Scb, Scrb, Scrib, ird, ird15, l(3)673, l(3)S042405, l(3)c00119, l(3)j7B3, scrb, smi97B, vart, scribbled, CG43398-PA, CG43398-PB, CG43398-PC, CG43398-PD, CG43398-PH, CG43398-PI, CG43398-PJ, CG43398-PK, CG43398-PL, CG43398-PM, CG43398-PN, CG43398-PO, CG43398-PP, CG43398-PQ, CG43398-PR, CG43398-PS, CG43398-PT, CG43398-PU, gp150-like, immune response deficient 15, lethal (3) c00119, scrib-PA, scrib-PB, scrib-PC, scrib-PD, scrib-PH, scrib-PI, scrib-PJ, scrib-PK, scrib-PL, scrib-PM, scrib-PN, scrib-PO, scrib-PP, scrib-PQ, scrib-PR, scrib-PS, scrib-PT, scrib-PU, scribble, scribbles, smell impaired 97B, vartul
Species: fruit fly
- Wu M, Pastor Pareja J, Xu T. Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature. 2010;463:545-8 pubmed publisher..5) and loss-of-function mutations in the conserved tumour suppressor scribbled (scrib) gives rise to metastatic tumours that display many characteristics observed in human cancers...
- Laprise P, Lau K, Harris K, Silva Gagliardi N, Paul S, Beronja S, et al. Yurt, Coracle, Neurexin IV and the Na(+),K(+)-ATPase form a novel group of epithelial polarity proteins. Nature. 2009;459:1141-5 pubmed publisher..We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus) is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity. ..
- Ma X, Li W, Yu H, Yang Y, Li M, Xue L, et al. Bendless modulates JNK-mediated cell death and migration in Drosophila. Cell Death Differ. 2014;21:407-15 pubmed publisher..Our results indicate that Ben constitutes an essential component of the evolutionarily conserved TNF-JNK pathway that modulates cell death and invasion, tumor progression, stress response and lifespan in metazoans. ..
- Igaki T, Pastor Pareja J, Aonuma H, Miura M, Xu T. Intrinsic tumor suppression and epithelial maintenance by endocytic activation of Eiger/TNF signaling in Drosophila. Dev Cell. 2009;16:458-65 pubmed publisher..In Drosophila imaginal epithelia, clones of cells mutant for tumor suppressors, such as scrib or dlg, lose their polarity and are eliminated by cell death...
- Hong Y, Stronach B, Perrimon N, Jan L, Jan Y. Drosophila Stardust interacts with Crumbs to control polarity of epithelia but not neuroblasts. Nature. 2001;414:634-8 pubmed..However, for the subset of ectodermal cells that delaminate and form neuroblasts, their polarity requires the function of Bazooka, but not of Stardust or Crumbs. ..
- Ma X, Yang L, Yang Y, Li M, Li W, Xue L. dUev1a modulates TNF-JNK mediated tumor progression and cell death in Drosophila. Dev Biol. 2013;380:211-21 pubmed publisher..Together, our data indicate that dUev1a encodes an essential component of the evolutionary conserved TNF-JNK signaling pathway that modulates tumor progression and cell death in metazoan. ..
- Froldi F, Ziosi M, Garoia F, Pession A, Grzeschik N, Bellosta P, et al. The lethal giant larvae tumour suppressor mutation requires dMyc oncoprotein to promote clonal malignancy. BMC Biol. 2010;8:33 pubmed publisher..Moreover, we show that dMyc abundance inside versus outside the mutant clones plays a key role in driving neoplastic overgrowth. ..
- Willoughby L, Schlosser T, Manning S, Parisot J, Street I, Richardson H, et al. An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discovery. Dis Model Mech. 2013;6:521-9 pubmed publisher..The platform can also be adapted for use with other disease models, thus offering widespread applications in drug development. ..
- Knust E, Bossinger O. Composition and formation of intercellular junctions in epithelial cells. Science. 2002;298:1955-9 pubmed..Comparisons between fly, worm, and vertebrate epithelia reveal marked similarities with respect to the molecules used, and pronounced differences in the organization of the junctions themselves. ..
- Krahn M, Bückers J, Kastrup L, Wodarz A. Formation of a Bazooka-Stardust complex is essential for plasma membrane polarity in epithelia. J Cell Biol. 2010;190:751-60 pubmed publisher..Our findings provide a molecular mechanism for the phosphorylation-dependent interaction between the Baz-PAR-3 and Crb complexes during the establishment of epithelial polarity. ..
- Wu V, Beitel G. A junctional problem of apical proportions: epithelial tube-size control by septate junctions in the Drosophila tracheal system. Curr Opin Cell Biol. 2004;16:493-9 pubmed..Possible tube-size functions of septate junctions include patterning of the apical extracellular matrix and regulation of conserved cell polarity genes such as Scribble and Discs Large.
- Laprise P, Paul S, Boulanger J, Robbins R, Beitel G, Tepass U. Epithelial polarity proteins regulate Drosophila tracheal tube size in parallel to the luminal matrix pathway. Curr Biol. 2010;20:55-61 pubmed publisher..Mutations in yurt (yrt) and scribble (scrib), which encode SJ-associated polarity proteins, cause an expansion of tracheal tubes but do not disrupt ..
- Igaki T, Pagliarini R, Xu T. Loss of cell polarity drives tumor growth and invasion through JNK activation in Drosophila. Curr Biol. 2006;16:1139-46 pubmed..Similar oncogenic cooperation mediated through these evolutionarily conserved signaling pathways could contribute to human cancer progression. ..
- Kanda H, Igaki T, Okano H, Miura M. Conserved metabolic energy production pathways govern Eiger/TNF-induced nonapoptotic cell death. Proc Natl Acad Sci U S A. 2011;108:18977-82 pubmed publisher..This result suggests a link between sensitivity to cell death and metabolic activity in cancer. ..
- Swanson L, Beitel G. Tubulogenesis: an inside job. Curr Biol. 2006;16:R51-3 pubmed
- Grzeschik N, Parsons L, Allott M, Harvey K, Richardson H. Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Curr Biol. 2010;20:573-81 pubmed publisher..Thus, our study implicates Lgl, aPKC, and Crumbs as regulators of tissue growth via the SWH pathway. ..
- Rolls M, Albertson R, Shih H, Lee C, Doe C. Drosophila aPKC regulates cell polarity and cell proliferation in neuroblasts and epithelia. J Cell Biol. 2003;163:1089-98 pubmed
- Mathew D, Gramates L, Packard M, Thomas U, Bilder D, Perrimon N, et al. Recruitment of scribble to the synaptic scaffolding complex requires GUK-holder, a novel DLG binding protein. Curr Biol. 2002;12:531-9 pubmed..Previous studies have revealed a genetic interaction between DLG and another PDZ scaffolding protein, SCRIBBLE (SCRIB), during the establishment of cell polarity in developing epithelia...
- Bilder D, Li M, Perrimon N. Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science. 2000;289:113-6 pubmed..b>Scribble (Scrib) is a cell junction-localized protein required for polarization of embryonic and, as demonstrated here, ..
- Wandler A, Guillemin K. Transgenic expression of the Helicobacter pylori virulence factor CagA promotes apoptosis or tumorigenesis through JNK activation in Drosophila. PLoS Pathog. 2012;8:e1002939 pubmed publisher..These data suggest a potential role for CagA-mediated JNK pathway activation in promoting gastric cancer progression. ..
- Leong G, Goulding K, Amin N, Richardson H, Brumby A. Scribble mutants promote aPKC and JNK-dependent epithelial neoplasia independently of Crumbs. BMC Biol. 2009;7:62 pubmed publisher..The Drosophila gene scribble (scrib) encodes a PDZ-domain scaffolding protein that regulates cell polarity and acts as a tumour suppressor in ..
- Külshammer E, Uhlirova M. The actin cross-linker Filamin/Cheerio mediates tumor malignancy downstream of JNK signaling. J Cell Sci. 2013;126:927-38 pubmed publisher..Our study identifies Cher as a new target of JNK signaling that links cytoskeleton dynamics to tumor progression. ..
- Harris K, Tepass U. Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis. J Cell Biol. 2008;183:1129-43 pubmed publisher..This study reveals functional interactions between apical polarity proteins and endocytosis that are critical for stabilizing dynamic basolateral AJs. ..
- Gorfinkiel N, Arias A. Requirements for adherens junction components in the interaction between epithelial tissues during dorsal closure in Drosophila. J Cell Sci. 2007;120:3289-98 pubmed..Our results show that regulated cell adhesion is a crucial element of the interactions that shape epithelial sheets in morphogenetic processes. ..
- Roche J, Packard M, Moeckel Cole S, Budnik V. Regulation of synaptic plasticity and synaptic vesicle dynamics by the PDZ protein Scribble. J Neurosci. 2002;22:6471-9 pubmedThe Drosophila tumor suppressor Scribble (Scrib) is a PDZ-containing protein required for maintaining epithelial cell polarity...
- Johnson K, Wodarz A. A genetic hierarchy controlling cell polarity. Nat Cell Biol. 2003;5:12-4 pubmed
- Albertson R, Doe C. Dlg, Scrib and Lgl regulate neuroblast cell size and mitotic spindle asymmetry. Nat Cell Biol. 2003;5:166-70 pubmed..Here we show that Discs large (Dlg), Scribble (Scrib) and Lethal giant larvae (Lgl) tumour suppressor proteins regulate multiple aspects of neuroblast ..
- Bilder D, Perrimon N. Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature. 2000;403:676-80 pubmed..Mutations in Drosophila scribble (scrib), which encodes a multi-PDZ (PSD-95, Discs-large and ZO-1) and leucine-rich-repeat protein, cause aberrant ..
- Pastor Pareja J, Wu M, Xu T. An innate immune response of blood cells to tumors and tissue damage in Drosophila. Dis Model Mech. 2008;1:144-54; discussion 153 pubmed publisher..Our findings reveal common mechanisms in the response to tumors and wounds in flies. A similar innate reaction may underlie the response to tumors and tissue damage in vertebrates and humans. ..
- Tanentzapf G, Tepass U. Interactions between the crumbs, lethal giant larvae and bazooka pathways in epithelial polarization. Nat Cell Biol. 2003;5:46-52 pubmed..These interactions extend to other genes within the crb (stardust, sdt) and lgl (discs large, dlg; scribble, scrib) pathways...
- Khoo P, Allan K, Willoughby L, Brumby A, Richardson H. In Drosophila, RhoGEF2 cooperates with activated Ras in tumorigenesis through a pathway involving Rho1-Rok-Myosin-II and JNK signalling. Dis Model Mech. 2013;6:661-78 pubmed publisher..Overall, our analysis highlights the need for further analysis of the Rok-Myosin-II pathway in cooperation with Ras in human cancers. ..
- Menut L, Vaccari T, Dionne H, Hill J, Wu G, Bilder D. A mosaic genetic screen for Drosophila neoplastic tumor suppressor genes based on defective pupation. Genetics. 2007;177:1667-77 pubmed..The isolation of additional loci that affect hyperplastic as well as neoplastic growth indicates the utility of this screening strategy for studying epithelial growth control. ..
- Doggett K, Grusche F, Richardson H, Brumby A. Loss of the Drosophila cell polarity regulator Scribbled promotes epithelial tissue overgrowth and cooperation with oncogenic Ras-Raf through impaired Hippo pathway signaling. BMC Dev Biol. 2011;11:57 pubmed publisher..Here we show in Drosophila that loss of Scribbled (Scrib), a cell polarity regulator and neoplastic tumor suppressor, results in impaired Hippo pathway signaling ..
- Brumby A, Goulding K, Schlosser T, Loi S, Galea R, Khoo P, et al. Identification of novel Ras-cooperating oncogenes in Drosophila melanogaster: a RhoGEF/Rho-family/JNK pathway is a central driver of tumorigenesis. Genetics. 2011;188:105-25 pubmed publisher..Collectively our analysis reveals the importance of the RhoGEF/Rho-family/JNK pathway in cooperative tumorigenesis with Ras(ACT). ..
- Rhiner C, López Gay J, Soldini D, Casas Tinto S, Martín F, Lombardia L, et al. Flower forms an extracellular code that reveals the fitness of a cell to its neighbors in Drosophila. Dev Cell. 2010;18:985-98 pubmed publisher..Cell-cell comparison of relative fwe(Lose) and fwe(ubi) levels ultimately determines which cell undergoes apoptosis. This "extracellular code" may constitute an ancient mechanism to terminate competitive conflicts among cells. ..
- Grifoni D, Garoia F, Schimanski C, Schmitz G, Laurenti E, Galle P, et al. The human protein Hugl-1 substitutes for Drosophila lethal giant larvae tumour suppressor function in vivo. Oncogene. 2004;23:8688-94 pubmedDrosophila lethal giant larvae: (lgl), discs large (dlg) and scribble (scrib) are tumour suppressor genes acting in a common pathway, whose loss of function leads to disruption of cell polarity and tissue architecture, uncontrolled ..
- Egger B, Boone J, Stevens N, Brand A, Doe C. Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe. Neural Dev. 2007;2:1 pubmed
- Uhlirova M, Jasper H, Bohmann D. Non-cell-autonomous induction of tissue overgrowth by JNK/Ras cooperation in a Drosophila tumor model. Proc Natl Acad Sci U S A. 2005;102:13123-8 pubmed..Benign lesions caused by loss of the neoplastic tumor suppressor gene scribble can efficiently be eliminated by JNK-induced apoptosis...
- Cordero J, Macagno J, Stefanatos R, Strathdee K, Cagan R, Vidal M. Oncogenic Ras diverts a host TNF tumor suppressor activity into tumor promoter. Dev Cell. 2010;18:999-1011 pubmed publisher..indicated that a TNF-dependent mechanism eliminates cells deficient for the polarity tumor suppressors dlg or scrib. In this study, however, we show that in tumors deficient for scrib that also expressed the Ras oncoprotein, the ..
- Tamori Y, Bialucha C, Tian A, Kajita M, Huang Y, Norman M, et al. Involvement of Lgl and Mahjong/VprBP in cell competition. PLoS Biol. 2010;8:e1000422 pubmed publisher..As far as we are aware, this is the first report that cell competition can occur in a mammalian cell culture system. ..
- Menendez J, Pérez Garijo A, Calleja M, Morata G. A tumor-suppressing mechanism in Drosophila involving cell competition and the Hippo pathway. Proc Natl Acad Sci U S A. 2010;107:14651-6 pubmed publisher..The formation of a tumor requires in addition the formation of a microenvironment that allows mutant cells to evade cell competition. ..
- Srivastava A, Pastor Pareja J, Igaki T, Pagliarini R, Xu T. Basement membrane remodeling is essential for Drosophila disc eversion and tumor invasion. Proc Natl Acad Sci U S A. 2007;104:2721-6 pubmed..Finally, although past efforts using MMP inhibitors have not yielded much success, our results strongly argue that BM modulation could be a critical target for cancer therapy. ..
- Lolo F, Casas Tinto S, Moreno E. Cell competition time line: winners kill losers, which are extruded and engulfed by hemocytes. Cell Rep. 2012;2:526-39 pubmed publisher..Therefore, engulfment is a consequence-not a cause-of loser cells' death...
- Thibault S, Singer M, Miyazaki W, Milash B, Dompe N, Singh C, et al. A complementary transposon tool kit for Drosophila melanogaster using P and piggyBac. Nat Genet. 2004;36:283-7 pubmed
- Bergstralh D, Haack T, St Johnston D. Epithelial polarity and spindle orientation: intersecting pathways. Philos Trans R Soc Lond B Biol Sci. 2013;368:20130291 pubmed publisher..In this review, we examine several factors implicated in both processes, namely Canoe, Bazooka, aPKC and Discs large, and consider the implications of this work on how the spindle is oriented during epithelial cell divisions. ..
- Lee C, Andersen R, Cabernard C, Manning L, Tran K, Lanskey M, et al. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev. 2006;20:3464-74 pubmed..We conclude that Aurora-A and Numb are novel inhibitors of neuroblast self-renewal and that spindle orientation regulates neuroblast self-renewal. ..
- Wu V, Schulte J, Hirschi A, Tepass U, Beitel G. Sinuous is a Drosophila claudin required for septate junction organization and epithelial tube size control. J Cell Biol. 2004;164:313-23 pubmed..null mutation suggests that sinuous functions in the same pathway as the septate junction genes neurexin and scribble, but that nervana 2, convoluted, varicose, and cystic have functions not shared by sinuous...
- Humbert P, Dow L, Russell S. The Scribble and Par complexes in polarity and migration: friends or foes?. Trends Cell Biol. 2006;16:622-30 pubmed..Recently, another set of proteins known as the Scribble complex (consisting of Scribble, Discs large and Lethal giant larvae) has also been shown to be important in ..
- Ohsawa S, Sugimura K, Takino K, Xu T, Miyawaki A, Igaki T. Elimination of oncogenic neighbors by JNK-mediated engulfment in Drosophila. Dev Cell. 2011;20:315-28 pubmed publisher..Drosophila imaginal epithelia, clones of cells mutant for evolutionarily conserved tumor suppressor genes such as scrib or dlg lose their epithelial integrity and are eliminated from epithelia when surrounded by wild-type tissue...
- Courbard J, Djiane A, Wu J, Mlodzik M. The apical/basal-polarity determinant Scribble cooperates with the PCP core factor Stbm/Vang and functions as one of its effectors. Dev Biol. 2009;333:67-77 pubmed publisher..The A/B determinant Scribble was found to interact both genetically and physically with Stbm/Vang...
- Turkel N, Sahota V, Bolden J, Goulding K, Doggett K, Willoughby L, et al. The BTB-zinc finger transcription factor abrupt acts as an epithelial oncogene in Drosophila melanogaster through maintaining a progenitor-like cell state. PLoS Genet. 2013;9:e1003627 pubmed publisher..screen for oncogenes capable of cooperating with the loss of the epithelial apico-basal cell polarity regulator, scribbled (scrib), and identified the cell fate regulator, Abrupt, a BTB-zinc finger protein...
- Jiang Y, Scott K, Kwak S, Chen R, Mardon G. Sds22/PP1 links epithelial integrity and tumor suppression via regulation of myosin II and JNK signaling. Oncogene. 2011;30:3248-60 pubmed publisher..with Ras overexpression; conversely, sds22 overexpression can largely suppress tumorigenic growth of Ras(V12)scrib(-/-) mutant cells...
- Brumby A, Richardson H. scribble mutants cooperate with oncogenic Ras or Notch to cause neoplastic overgrowth in Drosophila. EMBO J. 2003;22:5769-79 pubmed..We have used the MARCM system to generate mutant clones of the apical-basal cell polarity tumor suppressor gene, scribble, in the context of normal tissue...
- Grzeschik N, Amin N, Secombe J, Brumby A, Richardson H. Abnormalities in cell proliferation and apico-basal cell polarity are separable in Drosophila lgl mutant clones in the developing eye. Dev Biol. 2007;311:106-23 pubmed
- Zhao M, Szafranski P, Hall C, Goode S. Basolateral junctions utilize warts signaling to control epithelial-mesenchymal transition and proliferation crucial for migration and invasion of Drosophila ovarian epithelial cells. Genetics. 2008;178:1947-71 pubmed publisher..We identified two genes that encode known BLJ scaffolding proteins, lethal giant larvae (lgl) and scribble (scrib), and several not previously associated with BLJ function, including warts (wts) and roughened eye (roe), ..
- Uhlirova M, Bohmann D. JNK- and Fos-regulated Mmp1 expression cooperates with Ras to induce invasive tumors in Drosophila. EMBO J. 2006;25:5294-304 pubmedLoss of the epithelial polarity gene scribble in clones of Drosophila imaginal disc cells can cooperate with Ras signaling to induce malignant tumors...
- Sotillos S, Diaz Meco M, Caminero E, Moscat J, Campuzano S. DaPKC-dependent phosphorylation of Crumbs is required for epithelial cell polarity in Drosophila. J Cell Biol. 2004;166:549-57 pubmed..These results provide a mechanistic framework for the functional interaction between the Par-3-Par-6-aPKC and Crumbs-Sdt-Patj complexes based in the posttranslational modification of Crb by DaPKC. ..