期刊
CELLULAR SIGNALLING
卷 28, 期 9, 页码 1172-1185出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.cellsig.2016.05.014
关键词
p53-S-46 phosphorylation; p53-K-acetylations; miR34a; SIRT1; Bcl2; Proapoptotic genes
类别
资金
- National Research Foundation - Korean government (MSIP) [2013R1A2A2A01005056]
- National R&D Program for Cancer Control [131280]
- Health Technology R&D project, Ministry of Health and Welfare, Republic of Korea [A121725]
- National Research Foundation of Korea [2013R1A2A2A01005056] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Cellular senescence and apoptosis can be regulated by p53 activity, although the underlying mechanism of the switch between the two events remains largely unknown. Cells exposed to cancer chemotherapy can escape to senescence phenotype rather than undergoing apoptosis. By employing adenoviral transduction of p53 or TIS21 genes, we observed shifting of p53 induced-senescence to apoptosis in EJ bladder cancer cells, which express H-RasV12 and mutant p53; transduction of p53 increased H-RasV12 expression along with senescence phenotypes, whereas coexpression with TIS21 (p53 + TIS21) induced cell death rather than senescence. The TIS21-mediated switch of senescence to apoptosis was accompanied by nuclear translocation of p53 protein and its modifications on Ser-15 and Ser-46 phosphorylation and acetylations on Lys-120, -320, -373 and -382 residues. Mechanistically, TIS21/(BTG2) regulated postfranslational modification of p53 via enhancing miR34a and Bax expressions as opposed to inhibiting SIRT1 and Bc12 expression. At the same time, TIS21 increased APAF-1 and p53AIP1 expressions, but inhibited the interaction of p53 with iASPP. In vitro tumorigenicity was significantly reduced in the p53 + TIS21 expresser through inhibiting micro-colony proliferation by TIS21. Effect of TIS21 on the regulation of p53 activity was confirmed by knockdown of TIS21 expression by RNA interference. Therefore, we suggest TIS21 expression as an endogenous cell death inducer at the downstream of p53 gene, which might be useful for intractable cancer chemotherapy. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据