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

570 Citations (Scopus)

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

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Inborn Genetic Diseases
Tumor Suppressor Genes
Renal Cell Carcinoma
Nude Mice
Genes
Neoplasms
Carcinogenesis
Proteins
Transcription Factors
Carcinoma
Kidney

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

Cite this

Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. / Kondo, Keiichi; Klco, Jeff; Nakamura, Eijiro; Lechpammer, Mirna; Kaelin, William G.

In: Cancer Cell, Vol. 1, No. 3, 04.2002, p. 237-246.

Research output: Contribution to journalArticle

Kondo, Keiichi ; Klco, Jeff ; Nakamura, Eijiro ; Lechpammer, Mirna ; Kaelin, William G. / Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. In: Cancer Cell. 2002 ; Vol. 1, No. 3. pp. 237-246.
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