The positive regulation of p53 by the tumor suppressor VHL

Jae Seok Roe, Hong Duk Youn

Research output: Contribution to journalShort surveypeer-review

16 Citations (Scopus)


The ubiquitin-mediated degradation of hypoxia-inducible factor-α (HIF-α) by a von Hippel-Lindau tumor suppressor protein (pVHL) is mechanistically responsible for controlling gene expression due to oxygen availability. Germline mutations in the VHL gene cause dysregulation of HIF and induce an autosomal dominant cancer syndrome referred to as VHL disease. However, it is unclear whether HIF accumulation caused by VHL mutations is sufficient for tumorigenesis. Recently, we found that pVHL directly associates and positively regulates the tumor suppressor p53 by inhibiting Mdm2-mediated ubiquitination, and by subsequently recruiting p53-modifying enzymes. Moreover, VHL-deleted RCC cells showed attenuated apoptosis or abnormal cell-cycle arrest upon DNA damage, but became normal when pVHL was restored. Thus, pVHL appears to play a pivotal role in tumor suppression by participating actively as a component of p53 transactivation complex during DNA damage response.

Original languageEnglish
Pages (from-to)2054-2056
Number of pages3
JournalCell Cycle
Issue number18
Publication statusPublished - 2006 Sept 15

Bibliographical note

Funding Information:
This work was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Korea (0420010-2) to H.-D.Y.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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