具有多方面功能的 von Hippel-Lindau 肿瘤抑制蛋白。

The multifaceted von Hippel-Lindau tumour suppressor protein.

机构信息

Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Department of Biochemistry, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

出版信息

FEBS Lett. 2014 Aug 19;588(16):2704-11. doi: 10.1016/j.febslet.2014.02.026. Epub 2014 Feb 25.

DOI:10.1016/j.febslet.2014.02.026

PMID:24583008

Abstract

Loss of von Hippel-Lindau protein (pVHL) is known to contribute to the initiation and progression of tumours associated with VHL disease as well as certain sporadic tumours including clear cell renal cell carcinoma (ccRCC). The VHL gene was first identified and cloned over 20 years ago and our understanding of its functions and effects has significantly increased since then. The best-known function of pVHL is its role in promoting the degradation of hypoxia-inducible factor α subunit (HIFα) as part of an E3 ubiquitin ligase complex. HIF stabilisation and transcriptional activation are also associated with various epigenetic alterations, indicating a potential role for VHL loss with changes in the epigenome. This review will highlight current knowledge regarding pVHL as well as discuss potentially novel roles of pVHL and how these may impact on cancer progression.

摘要

众所周知，von Hippel-Lindau 蛋白（pVHL）的缺失会导致 VHL 疾病相关肿瘤以及某些散发性肿瘤（包括透明细胞肾细胞癌（ccRCC））的发生和发展。VHL 基因在 20 多年前被首次鉴定和克隆，自那时以来，我们对其功能和影响的理解已经大大增加。pVHL 最著名的功能是作为 E3 泛素连接酶复合物的一部分，促进缺氧诱导因子 α 亚基（HIFα）的降解。HIF 的稳定和转录激活也与各种表观遗传改变有关，这表明 VHL 缺失与表观基因组改变之间存在潜在的关系。这篇综述将重点介绍目前关于 pVHL 的知识，并讨论 pVHL 潜在的新作用以及这些作用如何影响癌症的进展。