p53 Stabilization and Transactivation by a von Hippel-Lindau Protein

Jae Seok Roe, Hyungsoo Kim, Soon Min Lee, Sung Tae Kim, Eun Jung Cho, Hong Duk Youn

Research output: Contribution to journalArticle

179 Citations (Scopus)

Abstract

von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. Although hypoxia-inducible factor-α (HIFα) is a well-documented substrate of von Hippel-Lindau tumor suppressor protein (pVHL), it remains unclear whether the dysregulation of HIF is sufficient to account for de novo tumorigenesis in VHL-deleted cells. Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53. Moreover, upon genotoxic stress, pVHL invoked an interaction between p53 and p300 and the acetylation of p53, which ultimately led to an increase in p53 transcriptional activity and p53-mediated cell cycle arrest and apoptosis. These results suggest that the tumor suppressor pVHL has an unexpected function to upregulate the tumor suppressor p53.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalMolecular Cell
Volume22
Issue number3
DOIs
Publication statusPublished - 2006 May 5

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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