A critical role for noncoding 5S rRNA in regulating Mdmx stability.

摘要: Both p53 and Mdmx are ubiquitinated degraded by the same E3 ligase Mdm2; interestingly, however, while is rapidly Mdm2, a stable protein in most cancer cells. Thus, mechanism which Mdm2 needs further elucidation. Here, we identified noncoding 5S rRNA as major component of Mdmx-associated complexes from human We show that acts natural inhibitor degradation Mdm2. RNAi-mediated knockdown endogenous rRNA, not affecting levels, significantly induces and, subsequently, activates p53-dependent growth arrest. Notably, binds RING domain blocks its ubiquitination whereas Mdm2-mediated remains intact. These results provide insights into differential effects on vivo reveal critical role for modulating p53-Mdmx axis.