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A Critical Role for Noncoding 5S rRNA in Regulating Mdmx Stability
- Source :
-
Molecular Cell . Sep2011, Vol. 43 Issue 6, p1023-1032. 10p. - Publication Year :
- 2011
-
Abstract
- Summary: Both p53 and Mdmx are ubiquitinated and degraded by the same E3 ligase Mdm2; interestingly, however, while p53 is rapidly degraded by Mdm2, Mdmx is a stable protein in most cancer cells. Thus, the mechanism by which Mdmx is degraded by Mdm2 needs further elucidation. Here, we identified the noncoding 5S rRNA as a major component of Mdmx-associated complexes from human cells. We show that 5S rRNA acts as a natural inhibitor of Mdmx degradation by Mdm2. RNAi-mediated knockdown of endogenous 5S rRNA, while not affecting p53 levels, significantly induces Mdmx degradation and, subsequently, activates p53-dependent growth arrest. Notably, 5S rRNA binds the RING domain of Mdmx and blocks its ubiquitination by Mdm2, whereas Mdm2-mediated p53 ubiquitination remains intact. These results provide insights into the differential effects on p53 and Mdmx by Mdm2 in vivo and reveal a critical role for noncoding 5S rRNA in modulating the p53-Mdmx axis. [Copyright &y& Elsevier]
- Subjects :
- *NON-coding RNA
*P53 protein
*LIGASES
*GENETIC regulation
*CANCER genetics
*PROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 10972765
- Volume :
- 43
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Molecular Cell
- Publication Type :
- Academic Journal
- Accession number :
- 65500500
- Full Text :
- https://doi.org/10.1016/j.molcel.2011.08.020