Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.

Published

Journal Article

Mdm2 regulates the p53 tumor suppressor by promoting its proteasome-mediated degradation. Mdm2 and p53 engage in an autoregulatory feedback loop that maintains low p53 activity in nonstressed cells. We now report that Mdm2 regulates p53 levels also by targeting ribosomal protein L26. L26 binds p53 mRNA and augments its translation. Mdm2 binds L26 and drives its polyubiquitylation and proteasomal degradation. In addition, the binding of Mdm2 to L26 attenuates the association of L26 with p53 mRNA and represses L26-mediated augmentation of p53 protein synthesis. Under nonstressed conditions, both mechanisms help maintain low cellular p53 levels by constitutively tuning down p53 translation. In response to genotoxic stress, the inhibitory effect of Mdm2 on L26 is attenuated, enabling a rapid increase in p53 synthesis. The Mdm2-L26 interaction thus represents an additional important component of the autoregulatory feedback loop that dictates cellular p53 levels and activity.

Full Text

Duke Authors

Cited Authors

  • Ofir-Rosenfeld, Y; Boggs, K; Michael, D; Kastan, MB; Oren, M

Published Date

  • October 2008

Published In

Volume / Issue

  • 32 / 2

Start / End Page

  • 180 - 189

PubMed ID

  • 18951086

Pubmed Central ID

  • 18951086

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

International Standard Serial Number (ISSN)

  • 1097-2765

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2008.08.031

Language

  • eng