Format

Send to:

Choose Destination
See comment in PubMed Commons below
Nat Cell Biol. 2003 Jan;5(1):64-70.

Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL.

Author information

  • 1Friedrich Miescher Institut, Maulbeerstrasse 66, Basel CH-4058, Switzerland.

Abstract

Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is linked to the development of haemangioblastomas in the central nervous system and retina, often in association with other tumours, such as clear-cell carcinomas of the kidney and phaeochromocytomas. Here we show that the VHL protein (pVHL) is a microtubule-associated protein that can protect microtubules from depolymerization in vivo. Both the microtubule binding and stabilization functions of pVHL depend on amino acids 95-123 of pVHL, a mutational 'hot-spot' in VHL disease. From analysis of naturally occurring pVHL mutants, it seems that only point mutations such as pVHL(Y98H) and pVHL(Y112H) (that predispose to haemangioblastoma and phaeochromocytoma, but not to renal cell carcinoma) disrupt pVHL's microtubule-stabilizing function. Our data identify a role for pVHL in the regulation of microtubule dynamics and potentially provide a link between this function of pVHL and the pathogenesis of haemangioblastoma and phaeochromocytoma in the context of VHL disease.

PMID:
12510195
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Write to the Help Desk