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

Publication ,  Journal Article
Ofir-Rosenfeld, Y; Boggs, K; Michael, D; Kastan, MB; Oren, M
Published in: Mol Cell
October 24, 2008

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.

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Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

October 24, 2008

Volume

32

Issue

2

Start / End Page

180 / 189

Location

United States

Related Subject Headings

  • Ubiquitination
  • Tumor Suppressor Protein p53
  • Ribosomal Proteins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-mdm2
  • Protein Biosynthesis
  • Proteasome Endopeptidase Complex
  • Models, Genetic
  • Mice
  • Humans
 

Citation

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Ofir-Rosenfeld, Y., Boggs, K., Michael, D., Kastan, M. B., & Oren, M. (2008). Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell, 32(2), 180–189. https://doi.org/10.1016/j.molcel.2008.08.031
Ofir-Rosenfeld, Yaara, Kristy Boggs, Dan Michael, Michael B. Kastan, and Moshe Oren. “Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.Mol Cell 32, no. 2 (October 24, 2008): 180–89. https://doi.org/10.1016/j.molcel.2008.08.031.
Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB, Oren M. Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 2008 Oct 24;32(2):180–9.
Ofir-Rosenfeld, Yaara, et al. “Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26.Mol Cell, vol. 32, no. 2, Oct. 2008, pp. 180–89. Pubmed, doi:10.1016/j.molcel.2008.08.031.
Ofir-Rosenfeld Y, Boggs K, Michael D, Kastan MB, Oren M. Mdm2 regulates p53 mRNA translation through inhibitory interactions with ribosomal protein L26. Mol Cell. 2008 Oct 24;32(2):180–189.
Journal cover image

Published In

Mol Cell

DOI

EISSN

1097-4164

Publication Date

October 24, 2008

Volume

32

Issue

2

Start / End Page

180 / 189

Location

United States

Related Subject Headings

  • Ubiquitination
  • Tumor Suppressor Protein p53
  • Ribosomal Proteins
  • RNA, Messenger
  • Proto-Oncogene Proteins c-mdm2
  • Protein Biosynthesis
  • Proteasome Endopeptidase Complex
  • Models, Genetic
  • Mice
  • Humans