GSBS Student Publications

Title

Regulation of the MDM2-p53 pathway by ribosomal protein L11 involves a post-ubiquitination mechanism

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Cancer Biology

Date

6-29-2006

Document Type

Article

Medical Subject Headings

Animals; Cell Line, Tumor; Humans; Mice; Proteasome Endopeptidase Complex; Protein Processing, Post-Translational; Proto-Oncogene Proteins c-mdm2; Ribosomal Proteins; Signal Transduction; Tumor Suppressor Protein p53; Ubiquitin; Ubiquitin-Protein Ligases

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Inhibition of the MDM2-p53 feedback loop is critical for p53 activation in response to cellular stresses. The ribosomal proteins L5, L11, and L23 can block this loop by inhibiting MDM2-mediated p53 ubiquitination and degradation in response to ribosomal stress. Here, we show that L11, but not L5 and L23, leads to a drastic accumulation of ubiquitinated and native MDM2. This effect is dependent on the ubiquitin ligase activity of MDM2, but not p53, and requires the central MDM2 binding domain (residues 51-108) of L11. We further show that L11 inhibited 26 S proteasome-mediated degradation of ubiquitinated MDM2 in vitro and consistently prolonged the half-life of MDM2 in cells. These results suggest that L11, unlike L5 and L23, differentially regulates the levels of ubiquitinated p53 and MDM2 and inhibits the turnover and activity of MDM2 through a post-ubiquitination mechanism.

Rights and Permissions

Citation: J Biol Chem. 2006 Aug 25;281(34):24304-13. Epub 2006 Jun 27. Link to article on publisher's site

DOI of Published Version

10.1074/jbc.M602596200

Related Resources

Link to article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID

16803902