Transcriptional regulation of human glycoprotein hormone common alpha subunit gene by CBP/p300 and p53

Xian Zhang, Roger Grand, Christopher McCabe, Jayne Franklyn, Phillip Gallimore, Andrew Turnell

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 alpha-subunit (alpha-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 12 S AdE1A inhibited a-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 a-subunit promoter. Akin to 12 S AdE1A, exogenous p53 expression repressed alpha-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 alpha-subunit activity. Stabilization of endogenous p53 by UV irradiation also correlated positively with reduced a-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 a-subunit activity.
Original languageEnglish
Pages (from-to)191-201
Number of pages11
JournalBiochemical Journal
Volume368
Issue number1
DOIs
Publication statusPublished - 15 Nov 2002

Keywords

  • SUG1
  • thyroid receptor
  • adenovirus E1A

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