Negative auto-regulators trap p53 in their web  

作　　者：Xiang Zhou Bo Cao Hua Lu 

机构地区：[1]Fudan University Shanghai Cancer Center and the Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China [2]Department of Biochemistry & Molecular Biology and Tulane Cancer Center, Tulane University School of Medicine, New Orleans, LA 70112, USA

出　　处：《Journal of Molecular Cell Biology》2017年第1期62-68,共7页分子细胞生物学报（英文版）

基　　金：H.L. was supported by NIH-NCl grants （RO1CA095441, ROlCA172468, R01CA127724, R21CA190775, and R21CA201889） as well as the Reynolds and Ryan Families Chair Fund. X.Z. was supported by the National Natural Science Foundation of China （no. 81672566）.

摘　　要：The transcriptional factor p53 activates the expression of a myriad of target genes involving a complicated signalling network, resulting in various cellular outcomes, such as growth arrest, senescence, apoptosis, and metabolic changes, and leading to con- sequent suppression of tumour growth and progression. Because of the profoundly adverse effect of p53 on growth and prolifer- ation of cancer cells, several feedback mechanisms have been employed by the cells to constrain p53 activity. Two major antagonists MDM2 and MDMX （the long forms） are transcriptionally induced by p53, but in return block p53 activity, forming a negative feedback circuit and rendering chemoresistance of several cancer cells. However, they are not alone, as cancer cells also employ other proteins encoded by p53 target genes to inhibit p53 activity at transcriptional, translational, and posttransla- tional levels. This essay is thus composed to review a recent progress in understanding the mechanisms for how cancer cells hijack the p53 autoregulation by these proteins for their growth advantage and to discuss the clinical implications of these auto- regulatory loops.

关 键 词：P53 MDM2 NGFR TRANSCRIPTION feedback loop CHEMORESISTANCE 

分 类 号：Q[生物学]