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The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer.
Open Biology ( IF 5.8 ) Pub Date : 2020-07-01 , DOI: 10.1098/rsob.200109
Giovanni Minervini 1 , Maria Pennuto 1, 2 , Silvio C E Tosatto 1
Affiliation  

The von Hippel–Lindau protein (pVHL) is a tumour suppressor mainly known for its role as master regulator of hypoxia-inducible factor (HIF) activity. Functional inactivation of pVHL is causative of the von Hippel–Lindau disease, an inherited predisposition to develop different cancers. Due to its impact on human health, pVHL has been widely studied in the last few decades. However, investigations mostly focus on its role in degrading HIFs, whereas alternative pVHL protein–protein interactions and functions are insistently surfacing in the literature. In this review, we analyse these almost neglected functions by dissecting specific conditions in which pVHL is proposed to have differential roles in promoting cancer. We reviewed its role in regulating phosphorylation as a number of works suggest pVHL to act as an inhibitor by either degrading or promoting downregulation of specific kinases. Further, we summarize hypoxia-dependent and -independent pVHL interactions with multiple protein partners and discuss their implications in tumorigenesis.



中文翻译:

pVHL 忽略了功能,这是癌症中缺氧依赖和独立调节的故事。

von Hippel-Lindau 蛋白 (pVHL) 是一种肿瘤抑制因子,主要以其作为缺氧诱导因子 (HIF) 活性的主要调节因子的作用而闻名。pVHL 的功能失活是 von Hippel-Lindau 病的原因,这是一种遗传易患不同癌症的倾向。由于对人类健康的影响,pVHL 在过去的几十年中得到了广泛的研究。然而,研究主要集中在其在降解 HIF 中的作用,而替代 pVHL 蛋白质-蛋白质相互作用和功能在文献中不断浮出水面。在这篇综述中,我们通过剖析 pVHL 在促进癌症中具有不同作用的特定条件来分析这些几乎被忽视的功能。我们回顾了它在调节磷酸化中的作用,因为许多工作表明 pVHL 通过降解或促进特定激酶的下调来充当抑制剂。此外,我们总结了缺氧依赖性和非依赖性 pVHL 与多种蛋白质伙伴的相互作用,并讨论了它们在肿瘤发生中的意义。

更新日期:2020-07-20
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