Document Detail


MCM proteins are negative regulators of hypoxia-inducible factor 1.
MedLine Citation:
PMID:  21658608     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
MCM proteins are components of a DNA helicase that plays an essential role in DNA replication and cell proliferation. However, MCM proteins are present in excess relative to origins of replication, suggesting they may serve other functions. Decreased proliferation is a fundamental physiological response to hypoxia in many cell types, and hypoxia-inducible factor 1 (HIF-1) has been implicated in this process. Here, we demonstrate that multiple MCM proteins bind directly to the HIF-1α subunit and synergistically inhibit HIF-1 transcriptional activity via distinct O(2)-dependent mechanisms. MCM3 inhibits transactivation domain function, whereas MCM7 enhances HIF-1α ubiquitination and proteasomal degradation. HIF-1 activity decreases when quiescent cells re-enter the cell cycle, and this effect is MCM dependent. Exposure to hypoxia leads to MCM2-7 downregulation in diverse cell types. These studies reveal a function of MCM proteins apart from their DNA helicase activity and establish a direct link between HIF-1 and the cell-cycle machinery.
Authors:
Maimon E Hubbi; Weibo Luo; Jin H Baek; Gregg L Semenza
Related Documents :
687898 - Does adipocyte hypercellularity in obesity exist?
10972178 - Identification of cells responding to vasoactive intestinal peptide by measuring intrac...
16172408 - Adp-ribosyl cyclases generate two unusual adenine homodinucleotides with cytotoxic acti...
6320968 - Intracellular localization of 2',3'-cyclic nucleotide 3'-phosphohydrolase in rat oligod...
18845488 - Can oligomeric t-cell receptor be used as a tool to detect viral peptide epitopes on in...
9753138 - In vitro and in vivo behaviour of ndf-expanded monkey schwann cells.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular cell     Volume:  42     ISSN:  1097-4164     ISO Abbreviation:  Mol. Cell     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-10     Completed Date:  2011-08-23     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  9802571     Medline TA:  Mol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  700-12     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Graduate Training Program in Cellular and Molecular Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors,  metabolism
Cell Cycle Proteins / physiology*
Cell Line
Gene Expression Regulation
HEK293 Cells
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors,  genetics*,  metabolism
Mice
NIH 3T3 Cells
Nuclear Proteins / physiology*
Oxygen / metabolism
Transcription, Genetic
Ubiquitination
Grant Support
ID/Acronym/Agency:
N01 HV028180/HV/NHLBI NIH HHS; N01-HV28180/HV/NHLBI NIH HHS; T32-GM008752/GM/NIGMS NIH HHS; T32-HL007525/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/Cell Cycle Proteins; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Nuclear Proteins; 7782-44-7/Oxygen
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Reversible inhibition of PSD-95 mRNA translation by miR-125a, FMRP phosphorylation, and mGluR signal...
Next Document:  Pathology, pathogenesis and molecular genetics of follicular NHL.