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Sci. STKE, 16 April 2002
Vol. 2002, Issue 128, p. tw137
[DOI: 10.1126/stke.2002.128.tw137]

EDITORS' CHOICE

Deubiquitination HAUSP Stabilizes p53

The tumor suppressor p53 is regulated by phosphorylation and controlled proteolysis by the ubiquitin-proteasome system. Li et al. show that herpesvirus-associated ubiquitin-specific protease (HAUSP) interacted with p53 and promoted its accumulation, even in conditions where the p53-ubiquitin ligase Mdm2 is overexpressed. Overexpression of HAUSP inhibited colony formation by lung carcinoma cells and inhibited growth of mouse embryo fibroblasts. This growth inhibition was dependent on the cells expressing p53. In addition to growth inhibition, HAUSP promoted p53-dependent apoptosis. HAUSP is a member of the ubiquitin-specific processing protease (UBP) family of deubiquitination enzymes (DUBs). The ability of HAUSP to influence p53 stability required the deubiquitinating activity and HAUSP decreased the detectable ubiquitinated p53 in Western blots. In an in vitro assay, HAUSP was able to directly deubiquitinate p53. In normal cells, the expression of a dominant-negative form of HAUSP that can bind p53, but not deubiquitinate it, resulted in accumulation of ubiquitinated p53 species (when the proteasome was inhibited). In addition, p53 was destabilized compared with that in cells that did not express the mutated HAUSP. The concentration of p53 appears to be regulated both by processes that promote ubiquitination and subsequent degradation and by processes that promote deubiquitination and subsequent stabilization.

M. Li, D. Chen, A. Shiloh, J. Luo, A. Y. Nikolaev, J. Qin, W. Gu, Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization. Nature 416, 648-653 (2002). [Online Journal]

Citation: HAUSP Stabilizes p53. Sci. STKE 2002, tw137 (2002).


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