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Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.

Recruitment of p300/CBP by the hypoxia-inducible factor, HIF-1, is essential for the transcriptional response to hypoxia and requires an interaction between the p300/CBP CH1 region and HIF-1alpha. A new p300-CH1 interacting protein, p35srj, has been identified and cloned. p35srj is an alternatively spliced isoform of MRG1, a human protein of unknown function. Virtually all endogenous p35srj is bound to p300/CBP in vivo, and it inhibits HIF-1 transactivation by blocking the HIF-1alpha/p300 CH1 interaction. p35srj did not affect transactivation by transcription factors that bind p300/CBP outside the CH1 region. Endogenous p35srj is up-regulated markedly by the HIF-1 activators hypoxia or deferoxamine, suggesting that it could operate in a negative-feedback loop. In keeping with this notion, a p300 CH1 mutant domain, defective in HIF-1 but not p35srj binding, enhanced endogenous HIF-1 function. In hypoxic cells, p35srj may regulate HIF-1 transactivation by controlling access of HIF-1alpha to p300/CBP, and may keep a significant portion of p300/CBP available for interaction with other transcription factors by partially sequestering and functionally compartmentalizing cellular p300/CBP.

Pubmed ID: 9887100


  • Bhattacharya S
  • Michels CL
  • Leung MK
  • Arany ZP
  • Kung AL
  • Livingston DM


Genes & development

Publication Data

January 1, 1999

Associated Grants


Mesh Terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Anoxia
  • Binding, Competitive
  • Cell Line
  • Cloning, Molecular
  • Conserved Sequence
  • DNA-Binding Proteins
  • Humans
  • Hypoxia-Inducible Factor 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunohistochemistry
  • Molecular Sequence Data
  • Nuclear Proteins
  • Protein Binding
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid
  • Trans-Activators
  • Transcription Factors
  • Transcriptional Activation