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PMID:9887100

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Citation

Bhattacharya, S, Michels, CL, Leung, MK, Arany, ZP, Kung, AL and Livingston, DM (1999) Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1. Genes Dev. 13:64-75

Abstract

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.

Links

PubMed PMC316375

Keywords

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

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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