Conditional modulation of glucocorticoid receptor activities by CREB-binding protein (CBP) and p300

Tomoshige Kino, Steven K. Nordeen, George P. Chrousos

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Coactivators of nuclear receptors are integral components of the signal transduction pathways of steroid hormones. Here, we show that one of the major coactivators of the glucocorticoid receptor (GR), CREB-binding protein (CBP), can also function conditionally as a negative regulator of its activities. Indeed, CBP suppressed the responsiveness of the mouse mammary tumor virus (MMTV) promoter to dexamethasone in a dose-dependent fashion in HeLa and A204 cells. Similarly, this protein suppressed the responsiveness of several glucocorticoid-responsive element (GRE)-containing synthetic promoters. Using deletion mutants of CBP, we localized the repressor effect of this protein to its N-terminal domain and showed that it was independent of the histone acetyltransferase and coactivator-binding domains but dependent upon its GR-binding domain. We also demonstrated functional differentiation between CBP and other coactivators, including SRC-1 and the CBP-related protein p300, both of which influenced GR signaling in a positive fashion. In fact, p300 completely antagonized the suppressive effects of CBP in a dose-dependent fashion, probably by competing with this protein at the level of the transcription complex. These findings suggest that CBP and p300 may function additively or antagonistically to each other depending on their relative concentrations and type of target tissue, to influence the sensitivity of tissues to glucocorticoids. Copyright (C) 1999.

Original languageEnglish
Pages (from-to)15-25
Number of pages11
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume70
Issue number1-3
DOIs
Publication statusPublished - Jul 1999
Externally publishedYes

Fingerprint

CREB-Binding Protein
Glucocorticoid Receptors
Modulation
Glucocorticoids
A 204
Proteins
Nuclear Receptor Coactivators
Steroid hormones
Tissue
Repressor Proteins
Mouse mammary tumor virus
Histone Acetyltransferases
Signal transduction
Transcription
Viruses
HeLa Cells
Carcinogens
Dexamethasone
Tumors
Signal Transduction

Keywords

  • Coactivator
  • CREB
  • Mouse mammary tumor virus (MMTV)
  • p300
  • SRC-1

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Conditional modulation of glucocorticoid receptor activities by CREB-binding protein (CBP) and p300. / Kino, Tomoshige; Nordeen, Steven K.; Chrousos, George P.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 70, No. 1-3, 07.1999, p. 15-25.

Research output: Contribution to journalArticle

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