The VHL tumor suppressor in development and disease: functional studies in mice by conditional gene targeting.

Abstract:

:The von Hippel-Lindau tumor suppressor pVHL plays a critical role in the pathogenesis of familial and sporadic clear cell carcinomas of the kidney and hemangioblastomas of the retina and central nervous system. pVHL targets the oxygen sensitive alpha subunit of hypoxia-inducible factor (HIF) for proteasomal degradation, thus providing a direct link between tumorigenesis and molecular pathways critical for cellular adaptation to hypoxia. Cell type specific gene targeting of VHL in mice has demonstrated that proper pVHL mediated HIF proteolysis is fundamentally important for survival, proliferation and differentiation of many cell types and furthermore, that inactivation of pVHL may, unexpectedly, inhibit tumor growth under certain conditions. Mouse knock out studies have provided novel mechanistic insights into VHL associated tumorigenesis and established a central role for HIF in the development of the VHL phenotype.

journal_name

Semin Cell Dev Biol

authors

Haase VH

doi

10.1016/j.semcdb.2005.03.006

subject

Has Abstract

pub_date

2005-08-01 00:00:00

pages

564-74

issue

4-5

eissn

1084-9521

issn

1096-3634

pii

S1084-9521(05)00052-2

journal_volume

16

pub_type

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