title: Regulation of microtubule stability by the von Hippel-Lindau tumour suppressor protein pVHL.
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.
authors.affiliation: Friedrich Miescher Institut, Maulbeerstrasse 66, Basel CH-4058, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hergovich
authors.forename: Joanna
authors.initials: J
authors.lastname: Lisztwan
authors.forename: Robert
authors.initials: R
authors.lastname: Barry
authors.forename: Pia
authors.initials: P
authors.lastname: Ballschmieter
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Krek
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D016147:Genes, Tumor Suppressor; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D008025:Ligases / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000502:physiology* / Q000648:ultrastructure*; D015739:Nocodazole / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000235:genetics*
chemical_list: D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human; D015739:Nocodazole