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Updated: Jul 15, 2026

Co-immunoprecipitation Assay Using Endogenous Nuclear Proteins from Cells Cultured Under Hypoxic Conditions
Published on: August 2, 2018
HIF-2alpha promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity
John D Gordan1, Jessica A Bertout, Cheng-Jun Hu
1Abramson Family Cancer Research Institute, School of Medicine, University of Pennsylvania, 421 Curie Boulevard, Philadelphia, PA 19104, USA.
Abstract:
HIF-2alpha promotes von Hippel-Lindau (VHL)-deficient renal clear cell carcinoma (RCC) tumorigenesis, while HIF-1alpha inhibits RCC growth. As HIF-1alpha antagonizes c-Myc function, we hypothesized that HIF-2alpha might enhance c-Myc activity. We demonstrate here that HIF-2alpha promotes cell-cycle progression in hypoxic RCCs and multiple other cell lines. This correlates with enhanced c-Myc promoter binding, transcriptional effects on both activated and repressed target genes, and interactions with Sp1, Miz1, and Max. Finally, HIF-2alpha augments c-Myc transformation of primary mouse embryo fibroblasts (MEFs). Enhanced c-Myc activity likely contributes to HIF-2alpha-mediated neoplastic progression following loss of the VHL tumor suppressor and influences the behavior of hypoxic tumor cells.
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