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-1α. 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-1α/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-1α 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.
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Dates
Type | When |
---|---|
Created | 17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.) |
Deposited | 3 years, 9 months ago (Nov. 14, 2021, 10:27 p.m.) |
Indexed | 1 week, 6 days ago (Aug. 23, 2025, 1:03 a.m.) |
Issued | 26 years, 8 months ago (Jan. 1, 1999) |
Published | 26 years, 8 months ago (Jan. 1, 1999) |
Published Online | 26 years, 8 months ago (Jan. 1, 1999) |
Published Print | 26 years, 8 months ago (Jan. 1, 1999) |
@article{Bhattacharya_1999, title={Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1}, volume={13}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.13.1.64}, DOI={10.1101/gad.13.1.64}, number={1}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Bhattacharya, Shoumo and Michels, Catherine L. and Leung, Man-Kit and Arany, Zoltàn P. and Kung, Andrew L. and Livingston, David M.}, year={1999}, month=jan, pages={64–75} }