ARID1A
AT rich interactive domain 1A (SWI-like)
member of human SWI-SNF complexes [Pubmed]
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role in cancer | TSG, fusion |
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global regulation of gene expression | ARID1A loss disrupts SWI/SNF targeting to enhancers to alter gene expression and drive tumorigenesis in colorectal cancer [Pubmed] |
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differentiation and development | ARID1A-depleted cells fail to undergo normal differentiation-associated cell cycle arrest [Pubmed] |
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types of alteration in cancer | frequent inactivating mutations in ovarian cancer, digestive tract cancers, bladder cancer [Pubmed]; recurrent R1989* in endometrioid carcinoma [Pubmed] |
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impact of mutation on function | in-frame deletions affecting the consensus nuclear export signal reduce steady-state protein levels of ARID1A, as it is rapidly degraded by the ubiquitin-proteasome system in the nucleus [Pubmed] |
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fusion partner | MAST2 in triple-negative breast cancer [Pubmed] |
genome instability and mutations
recruited to DNA double-strand breaks (DSB) via its interaction with the upstream DNA damage checkpoint kinase ATR, facilitates efficient processing of DSB to single-strand ends and sustains DNA damage signalling [Pubmed]
cell replicative immortality
ARID1A deficiency compromises ES cell pluripotency, severely inhibits self-renewal, and promotes differentiation into primitive endoderm-like cells [Pubmed]; negatively regulates TERT transcriptional regulation and activity via binding to the regulatory element of TERT, loss of ARID1A protein expression caused by inactivating mutations reactivates TERT transcriptional activity [Pubmed]
escaping programmed cell death
KD promoted proliferation and inhibited 5-fluorouracil-induced apoptosis in colon cancer SW480 cell line [Pubmed]; ARID1A LOF inactivates the apoptosis-promoting function of p53 by upregulating HDAC6, which directly deacetylates Lys120 of p53, a pro-apoptotic post-translational modification [Pubmed]
invasion and metastasis
represses hepatocellular carcinoma cell migration through lncRNA MVIH [Pubmed]
suppression of growth
re-expression in cells lacking functional ARID1A results in significant inhibition of colony formation in breast cancer T47D cell line [Pubmed]; KD in immortalised ovary epithelial cells is sufficient to enhance cellular proliferation and tumorigenicity [Pubmed]; silencing ARID1A expression significantly enhances cell growth rate in gastric epithelium GES1 cell line [Pubmed]; represses hepatocellular carcinoma cell proliferation through lncRNA MVIH in hepatocellular carcinoma [Pubmed]