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

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Kondo K,Klco J,Nakamura E,Lechpammer M,Kaelin WG Jr

doi

10.1016/s1535-6108(02)00043-0

keywords:

subject

Has Abstract

pub_date

2002-04-01 00:00:00

pages

237-46

issue

3

eissn

1535-6108

issn

1878-3686

pii

S1535610802000430

journal_volume

1

pub_type

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