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

被引：289

作者：

Hergovich, A ^{[1
]}

Lisztwan, J ^{[1
]}

Barry, R ^{[1
]}

Ballschmieter, P ^{[1
]}

Krek, W ^{[1
]}

机构：

[1] Friedrich Miescher Inst, CH-4058 Basel, Switzerland

来源：

NATURE CELL BIOLOGY | 2003年 / 5卷 / 01期

关键词：

D O I：

10.1038/ncb899

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：64 / 70

页数：7

共 42 条

[31] Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel-Lindau protein [J].