VHL and Hypoxia Signaling: Beyond HIF in Cancer.

VHL and Hypoxia Signaling: Beyond HIF in Cancer.
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DOI:
10.3390/biomedicines6010035
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发表时间:
2018-03-19
期刊:
影响因子:
4.7
通讯作者:
Zhang Q
Zhang Q
中科院分区:
工程技术3区
文献类型:
--
作者:
Zhang J;Zhang Q

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Von Hippel-Lindau (VHL)是一种重要的肿瘤抑制因子,在大多数肾透明细胞癌(ccRCC)中缺失。其调控途径涉及E3连接酶的活性,该连接酶靶向缺氧诱导因子α(包括HIF1α和HIF2α)降解蛋白酶体。近年来,越来越多的文献表明,VHL还具有其他与hif无关的功能。本文将重点综述最新发现的N-Myc下游调控基因3 (NDRG3)、AKT、G9a等vhl介导的信号通路及其在缺氧信号传导和肿瘤中的生理作用。我们还将讨论VHL和NF-κB信号之间的串扰。最后,我们将回顾针对VHL信号在癌症中的最新发现。
Von Hippel-Lindau (VHL) is an important tumor suppressor that is lost in the majority of clear cell carcinoma of renal cancer (ccRCC). Its regulatory pathway involves the activity of E3 ligase, which targets hypoxia inducible factor α (including HIF1α and HIF2α) for proteasome degradation. In recent years, emerging literature suggests that VHL also possesses other HIF-independent functions. This review will focus on VHL-mediated signaling pathways involving the latest identified substrates/binding partners, including N-Myc downstream-regulated gene 3 (NDRG3), AKT, and G9a, etc., and their physiological roles in hypoxia signaling and cancer. We will also discuss the crosstalk between VHL and NF-κB signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.
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