TY - JOUR
T1 - Cross-regulation of protein stability by p53 and nuclear receptor SHP
AU - Yang, Zhihong
AU - Zhang, Yuxia
AU - Kemper, Jongsook Kim
AU - Wang, Li
N1 - Copyright:
Copyright 2013 Elsevier B.V., All rights reserved.
PY - 2012/6/21
Y1 - 2012/6/21
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0039789
DO - 10.1371/journal.pone.0039789
M3 - Article
C2 - 22737255
AN - SCOPUS:84862700968
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e39789
ER -