Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

An ARF-independent c-MYC-activated tumor suppression pathway mediated by ribosomal protein-Mdm2 Interaction.

Cancer cell | Sep 14, 2010

http://www.ncbi.nlm.nih.gov/pubmed/20832751

In vitro studies have shown that inhibition of ribosomal biogenesis can activate p53 through ribosomal protein (RP)-mediated suppression of Mdm2 E3 ligase activity. To study the physiological significance of the RP-Mdm2 interaction, we generated mice carrying a cancer-associated cysteine-to-phenylalanine substitution in the zinc finger of Mdm2 that disrupted its binding to RPL5 and RPL11. Mice harboring this mutation, retain normal p53 response to DNA damage, but lack of p53 response to perturbations in ribosome biogenesis. Loss of RP-Mdm2 interaction significantly accelerates Eμ-Myc-induced lymphomagenesis. Furthermore, ribosomal perturbation-induced p53 response does not require tumor suppressor p19ARF. Collectively, our findings establish RP-Mdm2 interaction as a genuine p53 stress-signaling pathway activated by aberrant ribosome biogenesis and essential for safeguarding against oncogenic c-MYC-induced tumorigenesis.

Pubmed ID: 20832751 RIS Download

Mesh terms: Animals | DNA Damage | Genes, myc | Humans | Mice | Mice, Inbred C57BL | Mice, Transgenic | Protein Binding | Proto-Oncogene Proteins c-mdm2 | Proto-Oncogene Proteins c-myc | Ribosomal Proteins | Ribosomes | Signal Transduction | Tumor Suppressor Protein p14ARF | Tumor Suppressor Protein p53 | Zinc Fingers

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: K01 CA087580
  • Agency: NCI NIH HHS, Id: R01 CA100302
  • Agency: NCI NIH HHS, Id: R01 CA127770

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.