• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

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

Authors

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

Journal

Genes & development

Publication Data

January 1, 1999

Associated Grants

None

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