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Overexpression of SCYL1‐BP1 stabilizes functional p53 by suppressing MDM2‐mediated ubiquitination
Author(s) -
Yan Jing,
Di Yujun,
Shi Huili,
Rao Hai,
Huo Keke
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.09.019
Subject(s) - mdm2 , ubiquitin , regulator , suppressor , microbiology and biotechnology , chemistry , apoptosis , negative regulator , p53 protein , cancer research , biology , gene , signal transduction , biochemistry
Previously, we defined SCY1‐like 1 binding protein 1 (SCYL1‐BP1) to be a substrate of Pirh2 that binds to mouse double minute gene number 2 (MDM2). In the current study, we found that an increase in SCYL1‐BP1 protein levels caused a parallel change in the amount of p53 protein due to the inhibition by SCYL‐BP1 of MDM2‐mediated p53 ubiquitination. SCYL1‐BP1 was not able to alter the ubiquitination of p53 by human papillomavirus protein E6, indicating that the effect was specific for MDM2. Increases in the level of SCYL1‐BP1 protein in cells led to the greater transcriptional activation of p21 and gadd45, reduced rate of cellular proliferation, increased levels of apoptosis and inhibition of tumorigenicity. Thus, we propose that SCYL1‐BP1 is a novel regulator of the MDM2‐p53 feedback loop and that it may be a potential tumor suppressor.