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- Title
The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by disrupting the MDM2–DAXX–HAUSP complex.
- Authors
Min Sup Song; Su Jung Song; So Yeon Kim; Hyun Jung Oh; Dae-Sik Lim
- Abstract
The tumour suppressor p53, which accumulates in response to DNA damage and induces cell-cycle arrest and apoptosis, has a key function in the maintenance of genome integrity. Under normal conditions, the antiproliferative effects of p53 are inhibited by MDM2, a ubiquitin ligase that promotes p53 ubiquitination and degradation. MDM2 is also self-ubiquitinated and degraded. Here, we show that the tumour suppressor RASSF1A regulates G1–S cell-cycle progression in a p53-dependent manner by promoting MDM2 self-ubiquitination and preventing p53 degradation. Importantly, RASSF1A associates with MDM2 and death-domain-associated protein (DAXX) in the nucleus, thereby disrupting the interactions between MDM2, DAXX, and the deubiquitinase, HAUSP, and enhancing the self-ubiquitin ligase activity of MDM2. Moreover, RASSF1A partially contributes to p53-dependent checkpoint activation at early time points in response to DNA damage. These findings reveal a new and important function for RASSF1A in regulating the p53–MDM2 pathway.
- Publication
EMBO Journal, 2008, Vol 27, Issue 13, p1863
- ISSN
0261-4189
- Publication type
Academic Journal
- DOI
10.1038/emboj.2008.115