Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2003 Feb 21;278(8):6363-70. Epub 2002 Dec 17.

Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2.

Author information

1
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, People's Republic of China.

Abstract

Oncoprotein Mdm2 is a master negative regulator of the tumor suppressor p53 and has been recently shown to regulate the ubiquitination of beta-arrestin 2, an important adapter and scaffold in signaling of G-protein-coupled receptors (GPCRs). However, whether beta-arrestin 2 has any effect on the function of Mdm2 is still unclear. Our current results demonstrated that the binding of Mdm2 to beta-arrestin 2 was significantly enhanced by stimulation of GPCRs. Activation of GPCRs led to formation of a ternary complex of Mdm2, beta-arrestin 2, and GPCRs and thus recruited Mdm2 to GPCRs at plasma membrane. Moreover, the binding of beta-arrestin 2 to Mdm2 suppressed the self-ubiquitination of Mdm2 and consequently reduced the Mdm2-mediated p53 degradation and ubiquitination. Further experiments revealed that overexpression of beta-arrestin 2 enhanced the p53-mediated apoptosis while suppression of endogenous beta-arrestin 2 expression by RNA interference technology considerably attenuated the p53-mediated apoptosis. Our study thus suggests that beta-arrestin 2 may serve as a cross-talk linker between GPCR and p53 signaling pathways.

PMID:
12488444
DOI:
10.1074/jbc.M210350200
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire
    Loading ...
    Support Center