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

FEBS Lett. 2004 Jul 2;569(1-3):293-300. doi: 10.1016/j.febslet.2004.05.079.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Nuclear Proteins / metabolism
  • Protein Biosynthesis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • SUMO-1 Protein / genetics*
  • Sex Characteristics
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • DNA Primers
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Nuclear Proteins
  • RNA, Messenger
  • SUMO-1 Protein
  • Transcription Factors