Increase of SUMO-1 expression in response to hypoxia: direct interaction with HIF-1alpha in adult mouse brain and heart in vivo.
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.
Shao
Ruijin
R
Division of Endocrinology, Department of Physiology and Pharmacology, Göteborg University, SE-40530 Göteborg, Sweden.
Zhang
Fu-Ping
FP
Tian
Fei
F
Anders Friberg
P
P
Wang
Xiaoyang
X
Sjöland
Helen
H
Billig
Håkan
H
D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology*; D017931:DNA Primers; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025842:SUMO-1 Protein / Q000235:genetics*; D012727:Sex Characteristics; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
D017931:DNA Primers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D025842:SUMO-1 Protein; D014157:Transcription Factors