调节 p53 通路。

Modulating the p53 pathway.

机构信息

p53 Laboratory (A*STAR), 8A Biomedical Drive, Immunos, Singapore 138648, Singapore.

出版信息

Semin Cancer Biol. 2010 Feb;20(1):3-9. doi: 10.1016/j.semcancer.2010.02.004. Epub 2010 Mar 1.

DOI:10.1016/j.semcancer.2010.02.004

PMID:20193765

Abstract

p53 is a transcription factor that protects cells against stress, by modulating genes that induce growth arrest, repair, apoptosis, senescence or altered metabolism. Activation of p53 can potentially be used to modulate disease states. We describe here recent developments that attempt to modulate the function of p53 and outline strategies that are being investigated for pharmacological intervention in the p53 pathway. These include interruption of the interactions between p53 and its negative regulators, restabilization of mutant/misfolded p53, activation of p53 dependant transcription and modulation of p53 function systemically to affect the therapeutic profile of existing drugs. In addition the development of new animal models to investigate the above developments, including mice and zebrafish will be highlighted.

摘要

p53 是一种转录因子，通过调节诱导细胞生长停滞、修复、凋亡、衰老或改变代谢的基因来保护细胞免受应激。激活 p53 可能被用于调节疾病状态。我们在这里描述了最近的尝试调节 p53 功能的进展，并概述了正在研究的用于干预 p53 途径的药理学策略。这些策略包括中断 p53 与其负调节剂之间的相互作用、稳定突变型/错误折叠的 p53、激活 p53 依赖性转录以及系统性地调节 p53 功能以影响现有药物的治疗谱。此外，还将突出开发新的动物模型来研究上述进展，包括小鼠和斑马鱼。