國家衛生研究院 NHRI:Item 3990099045/5325
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    题名: Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability
    作者: Sheu, JJC;Guan, B;Choi, JH;Lin, A;Lee, CH;Hsiao, YT;Wang, TL;Tsai, FJ;Shih, IM
    贡献者: National Institute of Cancer Research
    摘要: Rsf-1 (HBXAP) has been reported as an amplified gene in human cancer, including the highly aggressive ovarian serous carcinoma. Rsf-1 protein interacts with SNF2H to form an ISWI chromatin remodeling complex, RSF. In this study, we investigated the functional role of Rsf-1 by observing phenotypes after expressing it in nontransformed cells. Acute expression of Rsf-1 resulted in DNA damage as evidenced by DNA strand breaks, nuclear gammaH2AX foci, and activation of the ATM-CHK2-p53-p21 pathway, leading to growth arrest and apoptosis. Deletion mutation and gene knockdown assays revealed that formation of a functional RSF complex with SNF2H was required for Rsf-1 to trigger DNA damage response (DDR). Gene knock-out of TP53 alleles, TP53 mutation, or treatment with an ATM inhibitor abolished up-regulation of p53 and p21 and prevented Rsf-1-induced growth arrest. Chronic induction of Rsf-1 expression resulted in chromosomal aberration and clonal selection for cells with c-myc amplification and CDKN2A/B deletion. Co-culture assays indicated Rsf-1-induced DDR as a selecting barrier that favored outgrowth of cell clones with a TP53 mutation. The above findings suggest that increased Rsf-1 expression and thus excessive RSF activity, which occurs in tumors harboring Rsf-1 amplification, can induce chromosomal instability likely through DDR.
    日期: 2010-12-03
    關聯: Journal of Biological Chemistry. 2010 Dec 3;285(49):38260-38269.
    Link to: http://dx.doi.org/10.1074/jbc.M110.138735
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000284625600034
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=78649681548
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