Please use this identifier to cite or link to this item:
https://doi.org/10.1074/jbc.M109.021824
DC Field | Value | |
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dc.title | Complex regulation of the transactivation function of hypoxia-inducible factor-1αby direct interaction with two distinct domains of the creb-binding protein/p300 | |
dc.contributor.author | Ruas, J.L. | |
dc.contributor.author | Berchner-Pfannschmidt, U. | |
dc.contributor.author | Malik, S. | |
dc.contributor.author | Gradin, K. | |
dc.contributor.author | Fandrey, J. | |
dc.contributor.author | Roeder, R.G. | |
dc.contributor.author | Pereira, T. | |
dc.contributor.author | Poellinger, L. | |
dc.date.accessioned | 2014-12-12T07:10:18Z | |
dc.date.available | 2014-12-12T07:10:18Z | |
dc.date.issued | 2010-01-22 | |
dc.identifier.citation | Ruas, J.L., Berchner-Pfannschmidt, U., Malik, S., Gradin, K., Fandrey, J., Roeder, R.G., Pereira, T., Poellinger, L. (2010-01-22). Complex regulation of the transactivation function of hypoxia-inducible factor-1αby direct interaction with two distinct domains of the creb-binding protein/p300. Journal of Biological Chemistry 285 (4) : 2601-2609. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M109.021824 | |
dc.identifier.issn | 00219258 | |
dc.identifier.uri | http://scholarbank.nus.edu.sg/handle/10635/115038 | |
dc.description.abstract | Activation of transcription in response to low oxygen tension is mediated by the hypoxia-inducible factor-1 (HIF-1). HIF-1 is a heterodimer of two proteins: aryl hydrocarbon receptor nuclear translocator and the oxygen-regulated HIF-1α. The C-terminal activation domain of HIF-1α has been shown to interact with cysteine/histidine-rich region 1 (CH1) of the coactivator CBP/p300 in a hypoxia-dependent manner. However, HIF forms lacking C-terminal activation domain (naturally occurring or genetically engineered) are still able to activate transcription of target genes in hypoxia. Here, we demonstrate that the N-terminal activation domain (N-TAD) of HIF-1α interacts with endogenous CBP and that this interaction facilitates its transactivation function. Our results show that interaction of HIF-1α N-TAD with CBP/p300 is mediated by the CH3 region of CBP known to interact with,among other factors, p53. Using fluorescence resonance energy transfer experiments, we demonstrate that N-TAD interacts with CH3 in vivo. Coimmunoprecipitation assays using endogenous proteins showed that immunoprecipitation of CBP in hypoxia results in the recovery of a larger fraction of HIF-1α than of p53. Chromatin immunoprecipitation demonstrated that at 1%O2 CBP is recruited to a HIF-1α but not to a p53 target gene. Upon activation of both pathways, lower levels of chromatin-associated CBP were detected at either target gene promoter. These results identify CBP as the coactivator directly interacting with HIF-1α N-TAD and mediating the transactivation function of this domain. Thus, we suggest that in hypoxia HIF-1α is a major CBP-interacting transcription factor that may compete with other CBP-dependent factors, including p53, for limiting amounts of this coactivator, underscoring the complexity in the regulation of gene expression by HIF-1α. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. | |
dc.description.uri | http://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1074/jbc.M109.021824 | |
dc.source | Scopus | |
dc.type | Article | |
dc.contributor.department | CANCER SCIENCE INSTITUTE OF SINGAPORE | |
dc.description.doi | 10.1074/jbc.M109.021824 | |
dc.description.sourcetitle | Journal of Biological Chemistry | |
dc.description.volume | 285 | |
dc.description.issue | 4 | |
dc.description.page | 2601-2609 | |
dc.description.coden | JBCHA | |
dc.identifier.isiut | 000273697800039 | |
Appears in Collections: | Staff Publications |
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