title: A critical role for noncoding 5S rRNA in regulating Mdmx stability.
abstract: 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.
authors.affiliation: Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, 1130 Saint Nicholas Avenue, New York, NY 10032, USA.
authors.forename: Muyang
authors.initials: M
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
mesh_terms: D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D012341:RNA, Ribosomal, 5S / Q000378:metabolism / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012341:RNA, Ribosomal, 5S