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.
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
Genes Dev.
Date: Jan. 01, 1999
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