SCRIB
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| Location (UCSC) | Chr 8: 143.79 – 143.82 Mb | Chr 15: 75.92 – 75.94 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
SCRIB, also known as Scribble, SCRIBL, or Scribbled homolog (Drosophila), is a scaffold
epithelial cells.[7][8] There is also strong evidence that SCRIB may play a role in cancer progression because of its strong homology to the Drosophila protein.[7]
Function
In homolog is a scaffold protein linked to cellular differentiation centered on the regulation of epithelial as well as neuronal morphogenesis. Deficiency in SCRIB impairs many aspects of cell polarity and cell movement. SCRIB is also likely involved in establishing apical-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.[8]
The transcribed protein products of the SCRIB gene along with
epithelial cells.[9] The precise mechanism by which these proteins function together is currently unknown, but they have been implicated in several signaling pathways, vesicle trafficking, and in the myosin II-actin cytoskeleton.[7] The Scribble complex has been shown to promote basolateral membrane identity by antagonizing both the Par complex and the Crumbs complex, which promote apical membrane identity.[9] 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.[7]
Structure
The human homolog is a LAP protein, it contains 16 leucine-rich repeats and four PDZ domains.[10] 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.[11]
Subcellular and tissue distribution
SCRIB is found in the cell membrane most often as a
epithelial cells.[13]
Clinical significance
The
Role as a tumor suppressor
As mentioned above, SCRIB has been identified as a tumor suppressor along with
MAP Kinase pathway by SCRIB.[16]
Role in epithelial mesenchymal transition (EMT)
Due to its role in
epithelial cells to become migratory and allowing these cells to adapt to as well as colonize new environments. In cancerous epithelial tissues, SCRIB is found primarily in the cytosol as opposed to its usual location in the membrane, thus further implicating a role in tumor progression and EMT for SCRIB.[17]
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
epithelial mesenchymal transition mediators was also observed in small lung adenocarcinoma cells that were depleted of SCRIB.[17]
References
- ^ a b c ENSG00000180900 GRCh38: Ensembl release 89: ENSG00000274287, ENSG00000180900 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022568 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Entrez Gene: SCRIB scribbled homolog (Drosophila)".
- PMID 8590280.
- ^ PMID 12766944.
- ^ PMID 17043654.
- ^ PMID 21617693.
- PMID 12499390.
- PMID 18716323.
- PMID 15649318.
- PMID 15806148.
- ^ PMID 11027293.
- PMID 19041750.
- PMID 18641685.
- ^ PMID 21549346.
- PMID 16344308.
Further reading
- Nakajima D, Okazaki N, Yamakawa H, et al. (2003). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Res. 9 (3): 99–106. PMID 12168954.
- Nagase T, Seki N, Tanaka A, et al. (1996). "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. PMID 8590280.
- 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. PMID 11027293.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. PMID 12477932.
- Dow LE, Brumby AM, Muratore R, et al. (2004). "hScrib is a functional homologue of the Drosophila tumour suppressor Scribble". Oncogene. 22 (58): 9225–30. PMID 14681682.
- Nakagawa S, Yano T, Nakagawa K, et al. (2004). "Analysis of the expression and localisation of a LAP protein, human scribble, in the normal and neoplastic epithelium of uterine cervix". Br. J. Cancer. 90 (1): 194–9. PMID 14710229.
- Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. S2CID 11683986.
- Brill LM, Salomon AR, Ficarro SB, et al. (2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Anal. Chem. 76 (10): 2763–72. PMID 15144186.
- Lehner B, Sanderson CM (2004). "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–23. PMID 15231747.
- Borg JP (2004). "[hScrib: a potential novel tumor suppressor]". Pathol. Biol. 52 (6): 328–31. PMID 15261375.
- Beausoleil SA, Jedrychowski M, Schwartz D, et al. (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. PMID 15302935.
- Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell. Proteomics. 3 (11): 1093–101. PMID 15345747.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. PMID 15489334.
- Petit MM, Meulemans SM, Alen P, et al. (2006). "The tumor suppressor Scrib interacts with the zyxin-related protein LPP, which shuttles between cell adhesion sites and the nucleus". BMC Cell Biol. 6 (1): 1. PMID 15649318.
- Barrios-Rodiles M, Brown KR, Ozdamar B, et al. (2005). "High-throughput mapping of a dynamic signaling network in mammalian cells". Science. 307 (5715): 1621–5. S2CID 39457788.
- Lahuna O, Quellari M, Achard C, et al. (2005). "Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway". EMBO J. 24 (7): 1364–74. PMID 15775968.
- Navarro C, Nola S, Audebert S, et al. (2005). "Junctional recruitment of mammalian Scribble relies on E-cadherin engagement". Oncogene. 24 (27): 4330–9. PMID 15806148.
- Métais JY, Navarro C, Santoni MJ, et al. (2005). "hScrib interacts with ZO-2 at the cell-cell junctions of epithelial cells". FEBS Lett. 579 (17): 3725–30. S2CID 4893407.
- Thomas M, Massimi P, Navarro C, et al. (2005). "The hScrib/Dlg apico-basal control complex is differentially targeted by HPV-16 and HPV-18 E6 proteins". Oncogene. 24 (41): 6222–30. PMID 16103886.
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