Cooperation between the ribosomal proteins L5 and L11 in the p53 pathway

Henning Horn, K. H. Vousden

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

MDM2 is a ubiquitin ligase that plays a key role in regulating the stability of the p53 tumor suppressor protein. Several proteins have been shown to activate the p53 pathway by interacting with and inhibiting the E3 function of MDM2, thereby leading to an accumulation of p53. These include the alternate reading frame (ARF) proteins and the ribosomal proteins L5 and L11. We found that when overexpressed alone, L11 is much less potent in inhibiting MDM2 than p14ARF. However, L11 cooperates with L5, resulting in a robust inhibition of the E3 activity of MDM2, and a stabilization and activation of p53 approaching that achieved by p14ARF. We further showed that the ability of L11 to bind the 5S rRNA is important for the cooperation with L5, and a mutant L11, which cannot bind the 5S rRNA, cannot cooperate with L5 in inhibiting MDM2.

Original languageEnglish
Pages (from-to)5774-5784
Number of pages11
JournalOncogene
Volume27
Issue number44
DOIs
Publication statusPublished - 2 Oct 2008
Externally publishedYes

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Keywords

  • L11
  • L5
  • MDM2
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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