一个故事有两面：pVHL 的 HIF 依赖性和 HIF 非依赖性功能。
Two sides to every story: the HIF-dependent and HIF-independent functions of pVHL.
机构信息
Departments of Medicine and Genetics, Division of Hematology/Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
出版信息
J Cell Mol Med. 2011 Feb;15(2):187-95. doi: 10.1111/j.1582-4934.2010.01238.x.
von Hippel-Lindau (VHL) disease is a hereditary cancer syndrome caused by inherited mutations that inactivate the VHL tumour suppressor gene. The VHL locus encodes pVHL, whose best studied function is to bind to and down-regulate the hypoxia-inducible factor (HIF) family of oxygen-dependent transcription factors. Early efforts have established the fundamental role of HIF in VHL-defective tumorigenesis and in particular renal cell carcinoma. However, recent findings have revealed an alternate side to the story, the HIF-independent tumour suppressor functions of pVHL. These include pVHL's ability to regulate apoptosis and senescence as well as its role in the maintenance of primary cilium and orchestrating the deposition of the extracellular matrix. To what extent these HIF-dependent and HIF-independent functions cooperate in VHL-defective tumorigenesis remains to be determined.
希佩尔-林道（VHL）病是一种遗传性癌症综合征，由失活 VHL 肿瘤抑制基因的遗传突变引起。VHL 基因座编码 pVHL，其研究最多的功能是与缺氧诱导因子（HIF）家族的氧依赖性转录因子结合并下调其功能。早期的研究已经确立了 HIF 在 VHL 缺陷性肿瘤发生中的基本作用，特别是在肾细胞癌中。然而，最近的研究结果揭示了这个故事的另一面，即 pVHL 的 HIF 非依赖性肿瘤抑制功能。这些功能包括 pVHL 调节细胞凋亡和衰老的能力，以及其在维持初级纤毛和协调细胞外基质沉积中的作用。这些 HIF 依赖性和 HIF 非依赖性功能在 VHL 缺陷性肿瘤发生中合作的程度仍有待确定。
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