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Hypoxia-inducible factor 1-mediated regulation of PPP1R3C promotes glycogen accumulation in human MCF-7 cells under hypoxia.

Abstract
Hundreds of genes can be regulated by hypoxia-inducible factor 1 (HIF1) under hypoxia. Here we demonstrated a HIF1-mediated induction of protein phosphatase 1, regulatory subunit 3C gene (PPP1R3C) in human MCF7 cells under hypoxia. By mutation analysis we confirmed the presence of a functional hypoxia response element that is located 229bp upstream from the PPP1R3C gene. PPP1R3C induction correlates with a significant glycogen accumulation in MCF7 cells under hypoxia. Knockdown of either HIF1α or PPP1R3C attenuated hypoxia-induced glycogen accumulation significantly. Knockdown of HIF2α reduced hypoxia-induced glycogen accumulation slightly (but not significantly). Our results demonstrated that HIF1 promotes glycogen accumulation through regulating PPP1R3C expression under hypoxia, which revealed a novel metabolic adaptation of cells to hypoxia.
AuthorsGuo-Min Shen, Feng-Lin Zhang, Xiao-Ling Liu, Jun-Wu Zhang
JournalFEBS letters (FEBS Lett) Vol. 584 Issue 20 Pg. 4366-72 (Oct 22 2010) ISSN: 1873-3468 [Electronic] England
PMID20888814 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Chemical References
  • Carrier Proteins
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Intracellular Signaling Peptides and Proteins
  • PPP1R3C protein, human
  • Glycogen
  • Phosphoprotein Phosphatases
  • Oxygen
Topics
  • Base Sequence
  • Blotting, Western
  • Carrier Proteins (genetics, metabolism)
  • Cell Hypoxia
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic (drug effects)
  • Glycogen (metabolism)
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
  • Intracellular Signaling Peptides and Proteins
  • Oxygen (pharmacology)
  • Phosphoprotein Phosphatases (genetics, metabolism)
  • Promoter Regions, Genetic (genetics)
  • RNA Interference
  • Response Elements (genetics)
  • Reverse Transcriptase Polymerase Chain Reaction

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