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VHL and Hypoxia Signaling: Beyond HIF in Cancer #MMPMID29562667
Zhang J; Zhang Q
Biomedicines 2018[Mar]; 6 (1): ä PMID29562667show ga
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 ? (including HIF1? and HIF2?) 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-?B signaling. Lastly, we will review the latest findings on targeting VHL signaling in cancer.