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Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo

Journal article
Authors Linus Ruijin Shao
F. P. Zhang
Fei Tian
P. Anders Friberg
Xiaoyang Wang
Helen Sjöland
Håkan Billig
Published in FEBS letters
Volume 569
Issue 1-3
Pages 293-300
ISSN 0014-5793 (Print)
Publication year 2004
Published at Wallenberg Laboratory
Institute of Physiology and Pharmacology, Dept of Physiology
Pages 293-300
Language en
Keywords Animals, Base Sequence, Brain/*metabolism, Cell Hypoxia/*physiology, DNA Primers, Female, Gene Expression Regulation/*physiology, Hypoxia-Inducible Factor 1, alpha Subunit, Male, Mice, Mice, Inbred C57BL, Myocardium/*metabolism, Nuclear Proteins/isolation & purification/metabolism, Protein Biosynthesis, RNA, Messenger/genetics/metabolism, Reverse Transcriptase Polymerase Chain Reaction, SUMO-1 Protein/*genetics, Sex Characteristics, Transcription Factors/*metabolism, Transcription, Genetic
Subject categories Medical and Health Sciences, Physiology


The present study investigates the regulation of small ubiquitin-related modifier-1 (SUMO-1) expression in response to hypoxia in adult mouse brain and heart. We observed a significant increase in SUMO-1 mRNAs and proteins after hypoxic stimulation in vivo. Because SUMO-1 interacts with various transcription factors, including hypoxia-inducible factor-1beta (HIF-1beta) in vitro, we not only demonstrated that the HIF-1alpha expression is increased by hypoxia in brain and heart, but also provided evidence that SUMO-1 co-localizes in vivo with HIF-1alpha in response to hypoxia by demonstrating the co-expression of these two proteins in neurons and cardiomyocytes. The specific interaction between SUMO-1 and HIF-1alpha was additionally demonstrated with co-immunoprecipitation. These results indicate that the increased levels of SUMO-1 participate in the modulation of HIF-1alpha function through sumoylation in brain and heart.

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