 |
English
|
正體中文
|
简体中文
|
Items with full text/Total items : 12145/12927 (94%)
Visitors : 848887
Online Users : 1396
|
|
|
Loading...
|
Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/5325
|
| Title: | Rsf-1, a chromatin remodeling protein, induces DNA damage and promotes genomic instability |
| Authors: | Sheu, JJC;Guan, B;Choi, JH;Lin, A;Lee, CH;Hsiao, YT;Wang, TL;Tsai, FJ;Shih, IM |
| Contributors: | National Institute of Cancer Research |
| Abstract: | 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. |
| Date: | 2010-12-03 |
| Relation: | 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 |
| Appears in Collections: | [李家惠] 期刊論文
|
Files in This Item:
| File |
Description |
Size | Format | |
|---|
| NCA2010121401.pdf | | 3369Kb | Adobe PDF | 814 | View/Open |
|
All items in NHRI are protected by copyright, with all rights reserved.
|
