We have investigated the functional interactions between adenovirus early region 1A (AdE1A) protein, the co-activators cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and SUG1, and the transcriptional repressor retinoblastoma (Rb) in mediating T3-dependent repression. Utilizing the human glycoprotein hormone common α-subunit (α-subunit) promoter and AdE1A mutants with selective binding capacity to these molecules we have determined an essential role for CBP/p300. In normal circumstances, wild-type 12S AdE1A inhibited α-subunit activity. In contrast, adenovirus mutants that retain both the SUG1- and Rb-binding sites, but lack the CBP/p300-binding site, were unable to repress promoter activity. We have also identified a role for the tumour-suppressor gene product p53 in regulation of the α-subunit promoter. Akin to 12S AdE1A, exogenous p53 expression repressed α-subunit activity. This function resided in the ability of p53 to interact with CBP/p300; an N-terminal mutant incapable of interacting with CBP/p300 did not inhibit α-subunit activity. Stabilization of endogenous p53 by UV irradiation also correlated positively with reduced α-subunit activity. Intriguingly, T3 stimulated endogenous p53 transcriptional activity, implicating p53 in T3-dependent signalling pathways. These data indicate that CBP/p300 and p53 are key regulators of α-subunit activity.
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November 2002
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Research Article|
November 15 2002
Transcriptional regulation of the human glycoprotein hormone common α subunit gene by cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and p53 Available to Purchase
Xian ZHANG;
Xian ZHANG
∗Cancer Research U.K. Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.,
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Roger J.A. GRAND;
Roger J.A. GRAND
∗Cancer Research U.K. Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.,
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Christopher J. McCABE;
Christopher J. McCABE
†Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
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Jayne A. FRANKLYN;
Jayne A. FRANKLYN
†Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.
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Phillip H. GALLIMORE;
Phillip H. GALLIMORE
∗Cancer Research U.K. Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.,
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Andrew S. TURNELL
Andrew S. TURNELL
1
∗Cancer Research U.K. Institute for Cancer Studies, The Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.,
1To whom correspondence should be addressed (e-mail [email protected]).
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Publisher: Portland Press Ltd
Received:
April 22 2002
Revision Received:
August 05 2002
Accepted:
August 07 2002
Accepted Manuscript online:
August 07 2002
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2002
2002
Biochem J (2002) 368 (1): 191–201.
Article history
Received:
April 22 2002
Revision Received:
August 05 2002
Accepted:
August 07 2002
Accepted Manuscript online:
August 07 2002
Citation
Xian ZHANG, Roger J.A. GRAND, Christopher J. McCABE, Jayne A. FRANKLYN, Phillip H. GALLIMORE, Andrew S. TURNELL; Transcriptional regulation of the human glycoprotein hormone common α subunit gene by cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and p53. Biochem J 15 November 2002; 368 (1): 191–201. doi: https://doi.org/10.1042/bj20020634
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