title: A novel VHLα isoform inhibits Warburg effect via modulation of PKM splicing.
abstract: Von Hippel-Lindau (VHL) is the most frequently mutated gene in clear cell renal carcinoma. Here, we identified a novel translational variant of VHL, termed VHLα, initiated from an alternative translational start site upstream and in frame with the ATG start codon. We showed that VHLα interacts with and regulates heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), which consequently modulates pyruvate kinase transcript splicing and reprograms cellular glucose metabolism. Our study demonstrated that a novel VHL isoform may function as a tumor suppressor through inhibiting the Warburg effect.
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, Beijing, 102206, China. yanbliu2012@sina.cn.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, 102206, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Yang
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: National Institute of Biological Sciences, Beijing, Beijing, 102206, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zuo
authors.affiliation: Collaborative Innovation Center of Cancer Medicine, National Institute of Biological Sciences, Beijing, Beijing, 102206, China. chengliang@nibs.ac.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D064113:CRISPR-Cas Systems; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006801:Humans; D047468:Immunoprecipitation; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D020033:Protein Isoforms; D011770:Pyruvate Kinase / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014407:Tumor Cells, Cultured; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D019344:Lactic Acid; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D011770:Pyruvate Kinase; C497446:VHL protein, human; D005947:Glucose
keywords: Alternative translation; Glucose metabolism; Pyruvate kinase; VHL; hnRNPA2B1