title: Ubiquitination is absolutely required for the degradation of hypoxia-inducible factor--1 alpha protein in hypoxic conditions.
abstract: The hypoxia-inducible factor (HIF) is recognized as the master regulator of hypoxia response. HIF-α subunits expression are tightly regulated. In this study, our data show that ts20 cells still expressed detectable E1 protein even at 39.5° C for 12 h, and complete depletion of E1 protein expression at 39.5° C by siRNA enhanced HIF-1α and P53 protein expression. Further inhibition of E1 at 39.5 °C by siRNA, or E1 inhibitor Ube1-41 completely blocked HIF-1α degradation. Moreover, immunoprecipitations of co-transfection of HA-ubiquitin and FLAG-HIF-1α plasmids directly confirmed the involvement of ubiquitin in the hypoxic degradation of HIF-1α. Additionally, hypoxic HIF-1 α degradation is independent of HAF, RACK1, sumoylation or nuclear/cytoplasmic localization. Taken together, our data suggest that constitutive HIF-1α protein degradation in hypoxia is absolutely ubiquitination-dependent, and unidentified E3 ligase may exist for this degradation pathway.
authors.affiliation: Department of Urology, Linzi District People's Hospital, Zibo, 255400, China.
authors.forename: Ronghai
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Gynecology, Qingdao Municipal Hospital, Qingdao, 266011, China. Electronic address: zpskx001@163.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, Qingdao Municipal Hospital, Qingdao, 266011, China.
authors.forename: Jinhang
authors.initials: J
authors.lastname: Li
authors.affiliation: Laboratory Department, School of Medicine, Qingdao University, Qingdao, 266071, China.
authors.forename: Hongzai
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Hepatobiliary Surgery, Qingdao Municipal Hospital, Qingdao, 266071, China. Electronic address: qdmhshigj@yahoo.com.
authors.forename: Guangjun
authors.initials: G
authors.lastname: Shi
mesh_terms: D015687:Cell Hypoxia / Q000502:physiology; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D025801:Ubiquitin; D010100:Oxygen
keywords: Degradation; Hypoxia; Hypoxia-inducible factor; Ubiquitin