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Biomedicines 2018, 6(1), 35;

VHL and Hypoxia Signaling: Beyond HIF in Cancer

Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, UNC-Chapel Hill, Chapel Hill, NC 27599, USA
Department of Pharmacology, UNC-Chapel Hill, Chapel Hill, NC 27599, USA
Authors to whom correspondence should be addressed.
Received: 24 February 2018 / Revised: 12 March 2018 / Accepted: 16 March 2018 / Published: 19 March 2018
(This article belongs to the Special Issue Hypoxia)
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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. View Full-Text
Keywords: VHL; Hypoxia; ccRCC VHL; Hypoxia; ccRCC

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Zhang, J.; Zhang, Q. VHL and Hypoxia Signaling: Beyond HIF in Cancer. Biomedicines 2018, 6, 35.

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