SCRIB: Difference between revisions
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== Function == |
== Function == |
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In [[Drosophila melanogaster]], SCRIB is involved in synaptic function, nueroblast differentiation, and epithelial polarization. Deficiency in SCRIB impairs many aspects of [[Cell_migration#Cell_polarity|cell polarity]] and [[cell migration|cell movement]]. SCRIB is also likely involved in establishing apico-basal polarity as well as progression from the [[G1 phase]] to [[S phase]] in the [[cell cycle]] as a result of its relationship with [[cell proliferation]] and [[exocytosis]]. Mechanistically, the human [[homolog]] is a scaffold protein linked to [[cellular differentiation]] centered on the regulation of epithelial as well as neuronal morphogenesis. |
In [[Drosophila melanogaster]], SCRIB is involved in synaptic function, nueroblast differentiation, and epithelial polarization. Deficiency in SCRIB impairs many aspects of [[Cell_migration#Cell_polarity|cell polarity]] and [[cell migration|cell movement]]. SCRIB is also likely involved in establishing apico-basal polarity as well as progression from the [[G1 phase]] to [[S phase]] in the [[cell cycle]] as a result of its relationship with [[cell proliferation]] and [[exocytosis]]. <ref name="PMID: 17043654">{{cite journal | author =L E Dow, J S Kauffman, J Caddy, A S Peterson, S M Jane, S M Russell and P O Humbert | title = The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge | journal = Oncogene | volume = 26 | issue = 16 | pages = 2272–82 | year = 2007 | month = April | pmid = 17043654 | }}</ref> Mechanistically, the human [[homolog]] is a scaffold protein linked to [[cellular differentiation]] centered on the regulation of epithelial as well as neuronal morphogenesis. |
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== Structure == |
== Structure == |
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Revision as of 17:39, 1 April 2013
Template:PBB Scribbled homolog (Drosophila), also known as SCRIB, is a protein which in humans is encoded by the SCRIB gene.[1][2]
Function
In Drosophila melanogaster, SCRIB is involved in synaptic function, nueroblast differentiation, and epithelial polarization. Deficiency in SCRIB impairs many aspects of cell polarity and cell movement. SCRIB is also likely involved in establishing apico-basal polarity as well as progression from the G1 phase to S phase in the cell cycle as a result of its relationship with cell proliferation and exocytosis. [3] Mechanistically, the human homolog is a scaffold protein linked to cellular differentiation centered on the regulation of epithelial as well as neuronal morphogenesis.
Structure
The human homolog contains 16 leucine-rich repeats and four PDZ domains. SCRIB belongs to a protein complex containing betaPIX, an exchange factor for Rac/Cdc42, and GIT1, a GTPase activating protein for ARF6 implicated in receptor recycling and exocytosis.[4]
Location
SCRIB is found in the cell membrane most often as a peripheral membrane protein. It is also found in cellular junctions such as adherens junctions and tight junctions.[5] Specifically, it is located in the kidney, skeletal muscles, liver, lung, breast, intestine, placenta and epithelial cells. [6]
Clinical significance
The PDZ domain of SCRIB binds directly to the human papillomavirus E6 protein.[7] SCRIB is targeted for ubiquitination by a complex of E6 and UBE3A and E6 induces degradation of SCRIB.[7]
Role in Cancer
Along with Dlg (Discs large) and Lgl (Lethal giant larvae), SCRIB has been linked to a common genetic pathway that plays a role in cell polarity and cell proliferation in epithelial cells. These genes have also been identified as tumor suppressors in Drosophila Melanogaster. Since these genes are highly conserved in humans, there is evidence that they play a role in cancer progression. [8]
SCRIB inhibits breast cancer formation and depletion of SCRIB promotes neoplastic growth by disrupting morphogenesis and inhibiting cell death.[9]
SCRIB has also been implicated in epithelial mesenchymal transition, which is linked to tumor metastasis and proliferation in many cancers. Knockdown mutants have resulted in the loss of adhesion between Madin-Darby canine kidney epithelial cells. This loss of adhesion was correlated with an acquired mesenchymal appearance, an increase in motility, and loss of directionality. These effects were a direct result of the interruption of E-cadherin-mediated cellular adhesion. This supports the idea that SCRIB can act as a tumor suppressor and also supports that the loss of function of SCRIB can lead to epithelial mesenchymal transition. [10]
References
- ^ "Entrez Gene: SCRIB scribbled homolog (Drosophila)".
- ^ Nagase T, Seki N, Tanaka A, Ishikawa K, Nomura N (1995). "Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1". DNA Res. 2 (4): 167–74, 199–210. doi:10.1093/dnares/2.4.167. PMID 8590280.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ L E Dow, J S Kauffman, J Caddy, A S Peterson, S M Jane, S M Russell and P O Humbert (2007). "The tumour-suppressor Scribble dictates cell polarity during directed epithelial migration: regulation of Rho GTPase recruitment to the leading edge". Oncogene. 26 (16): 2272–82. PMID 17043654.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, Navarro C, Rachel R, Montcouquiol M, Sans N, Etienne-Manneville S, Borg JP, Santoni MJ (2008). "Scrib regulates PAK activity during the cell migration process". Hum. Mol. Genet. 17 (22): 3552–65. doi:10.1093/hmg/ddn248. PMID 18716323.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Petit MM, Meulemans SM, Alen P, Ayoubi TA, Jansen E, Van de Ven WJ. (2005). "The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus". BMC Cell Biol. 6. PMID 15649318.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Navarro C, Nola S, Audebert S, Santoni MJ, Arsanto JP, Ginestier C, Marchetto S, Jacquemier J, Isnardon D, Le Bivic A, Birnbaum D, Borg JP. (2005). "Junctional recruitment of mammalian Scribble relies on E-cadherin engagement". Oncogene. 24 (27): 4330–9. PMID 15806148.
{{cite journal}}: Cite has empty unknown parameters:|1=and|2=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ a b Nakagawa S, Huibregtse JM (2000). "Human scribble (Vartul) is targeted for ubiquitin-mediated degradation by the high-risk papillomavirus E6 proteins and the E6AP ubiquitin-protein ligase". Mol. Cell. Biol. 20 (21): 8244–53. doi:10.1128/MCB.20.21.8244-8253.2000. PMC 86433. PMID 11027293.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Patrick Humbert, Sarah Russell, Helena Richardson (2003). "Dlg, Scribble and Lgl in cell polarity, cell proliferation and cancer". Bio Essays. 25 (6): 542–53. PMID 12766944.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Zhan L, Rosenberg A, Bergami KC, Yu M, Xuan Z, Jaffe AB, Allred C, Muthuswamy SK (2008). "Deregulation of scribble promotes mammary tumorigenesis and reveals a role for cell polarity in carcinoma". Cell. 135 (5): 865–78. doi:10.1016/j.cell.2008.09.045. PMID 19041750.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Yi Qin, Christopher Capaldo, Barry M. Gumbiner, and Ian G. Macara (2005). "The mammalian SCRIB polarity protein regulates epithelial cell adhesion and migration through E-cadherin". JCB. 171 (6): 1061–71. PMID 16344308.
{{cite journal}}: Cite has empty unknown parameter:|1=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
Further reading
PDB gallery | |
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