Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The von Hippel-Lindau tumor suppressor (pVHL) targets hydroxylated alpha-subunits of hypoxia-inducible factor (HIF) for ubiquitin-mediated proteasomal destruction through direct interaction with the hydroxyproline binding pocket in its beta-domain. Although disruption of this process may contribute to VHL-associated tumor predisposition by up-regulation of HIF target genes, genetic and biochemical analyses support the existence of additional functions, including a role in the assembly of extracellular matrix. In an attempt to delineate these pathways, we searched for novel pVHL-binding proteins. Here we report a direct, hydroxylation-dependent interaction with alpha-chains of collagen IV. Interaction with pVHL was also observed with fibrillar collagen chains, but not the folded collagen triple helix. The interaction was suppressed by a wide range of tumor-associated mutations, including those that do not disturb the regulation of HIF, supporting a role in HIF-independent tumor suppressor functions.

Original publication

DOI

10.1074/jbc.M611648200

Type

Journal article

Journal

J Biol Chem

Publication Date

04/05/2007

Volume

282

Pages

13264 - 13269

Keywords

Animals, Basic Helix-Loop-Helix Transcription Factors, Binding Sites, Cell Line, Collagen Type IV, Extracellular Matrix, Humans, Hydroxylation, Hydroxyproline, Neoplasms, Proteasome Endopeptidase Complex, Protein Binding, Ubiquitin, Von Hippel-Lindau Tumor Suppressor Protein