Molecular Info® Copy Right © 2001
Institute of Molecular Development LLC
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Deubiquitination of p53 by HAUSP is an important
pathway for p53 stabilization
MUYANG LI, DELIN CHEN, ARIEL SHILOH, JIANYUAN LUO, ANATOLY Y. NIKOLAEV, JUN QIN & WEI GU
The Nature, April 2002, 416: 648 - 653.
The p53 tumour suppressor is a short-lived protein that is maintained at low levels in
normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis. Stabilization
of p53 is crucial for its tumour suppressor function. By
mass spectrometry of affinity-purified p53-associated factors,
herpesvirus-associated ubiquitin-specific protease (HAUSP) as a novel p53-interacting
protein was identified. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also
induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has
an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in
vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells
increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an
important mechanism by which p53 can be stabilized by direct deubiquitination and also
imply that HAUSP might function as a tumour suppressor in vivo through the stabilization
of p53.
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