MDMX公司
平方毫米
细胞凋亡
DNA损伤
生物
癌症研究
体细胞
抑制器
细胞生物学
转录因子
基因
细胞周期检查点
细胞周期
遗传学
DNA
作者
Erik Meulmeester,Aart G. Jochemsen
出处
期刊:Current Cancer Drug Targets
[Bentham Science]
日期:2008-03-01
卷期号:8 (2): 87-97
被引量:154
标识
DOI:10.2174/156800908783769337
摘要
Approximately 50% of sporadic human tumors harbor somatic mutations in the p53 gene locus, while germ line mutations confer a high familial risk and are associated with Li-Fraumeni Syndrome patients. The p53 tumor suppressor protein is often referred to as the “guardian of the genome” since its response to DNA-damage or checkpoint failure gives rise to a series of anti-proliferative responses. One of the most important functions of p53 is its ability to induce apoptosis, while disruption of this route can promote tumor progression and chemo resistance. Besides its ability to promote apoptosis through transcription dependent mechanisms, p53 may also be able to activate apoptosis independent of transcriptional regulation. Therefore, to ensure normal cell growth, p53 levels and activity are tightly regulated. Upon diverse forms of cellular stress the steady state levels and transcriptional activity of p53 are considerably increased. The stabilization and activation of p53 are a result of hindered inhibition by its negative regulators, e.g. Mdmx (also known as Mdm4) and Mdm2, while on the other hand activators such as HIPK2 and DYRK2 enhance the p53 response. The continually increasing understanding of the mechanisms of regulation of p53 may provide the basis for new drug designs that could eventually lead to therapeutics to reactivate p53 in cancers. Keywords: p53, apoptosis, Mdm2, Mdmx, Bcl2-proteins, HIPK2, DYRK2, Nutlin3, RITA
科研通智能强力驱动
Strongly Powered by AbleSci AI