Cross-Regulation of Protein Stability by p53 and Nuclear Receptor SHP

被引:9
|
作者
Yang, Zhihong [1 ,2 ]
Zhang, Yuxia [1 ,2 ]
Kemper, Jongsook Kim [3 ]
Wang, Li [1 ,2 ]
机构
[1] Univ Utah, Sch Med, Dept Med, Huntsman Canc Inst, Salt Lake City, UT 84112 USA
[2] Univ Utah, Sch Med, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA
[3] Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL USA
来源
PLOS ONE | 2012年 / 7卷 / 06期
关键词
SMALL HETERODIMER PARTNER; NEGATIVE FEEDBACK-REGULATION; FATTY-ACID SYNTHASE; DIURNAL REGULATION; GENE-EXPRESSION; LIVER RECEPTOR; X RECEPTOR; ERR-GAMMA; INHIBITION; GROWTH;
D O I
10.1371/journal.pone.0039789
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
We report here a novel interplay between tumor suppressor p53 and nuclear receptor SHP that controls p53 and SHP stability. Overexpression of p53 causes rapid SHP protein degradation, which does not require the presence of Mdm2 and is mediated by the proteosome pathway. Overexpressing SHP alone does not affect p53 stability. However, SHP destabilizes p53 by augmentation of Mdm2 ubiquitin ligase activity toward p53. The single amino acid substitution in the SHP protein SHPK170R increases SHP binding to p53 relative to SHP wild-type, whereas SHPG171A variant shows a diminished p53 binding. As a result of the cross-regulation, the tumor suppressor function of p53 and SHP in inhibition of colon cancer growth is compromised. Our findings reveal a unique scenario for a cross-inhibition between two tumor suppressors to keep their expression and function in check.
引用
收藏
页数:8
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