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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

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

doi

10.1101/gad.13.1.64

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

64-75

issue

1

eissn

0890-9369

issn

1549-5477

journal_volume

13

pub_type

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