Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein

Keiichi Kondo, Jeff Klco, Eijiro Nakamura, Mirna Lechpammer, William G. Kaelin

Research output: Contribution to journalArticle

596 Scopus citations

Abstract

Inactivation of the von Hippel-Lindau tumor suppressor gene is linked to the development of hereditary (VHL Disease-associated) and sporadic clear cell carcinoma of the kidney. The VHL gene product, pVHL, targets the heterodimeric transcription factor HIF for polyubiquitination, and restoration of pVHL function in VHL-/- renal carcinoma cells suppresses their ability to form tumors in nude mice. Here we show that tumor suppression by pVHL can be overridden by a HIF variant that escapes pVHL control. These studies prove that HIF is a critical downstream target of pVHL and establish that activation of HIF target genes can promote tumorigenesis in vivo.

Original languageEnglish (US)
Pages (from-to)237-246
Number of pages10
JournalCancer Cell
Volume1
Issue number3
DOIs
StatePublished - Apr 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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