Nuclear Factor of Activated T Cells (NFAT)-dependent Transactivation Regulated by the Coactivators p300/CREB-binding Protein (CBP)

doi:10.1084/jem.187.12.2031

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J. Exp. Med., Volume 187, Number 12, June 15, 1998 2031-2036

Nuclear Factor of Activated T Cells (NFAT)-dependent Transactivation Regulated by the Coactivators p300/CREB-binding Protein (CBP)

By Carmen García-Rodríguez and Anjana Rao

From the Department of Pathology, Harvard Medical School, and the Center for Blood Research, Boston, Massachusetts 02115

p300 and cAMP response element-binding protein (CREB)-binding protein (CBP) are members of a family of coactivators involvedin the regulation of transcription and chromatin. We show thattranscription factors of the nuclear factor of activated T cells(NFAT) family bind p300/CBP and recruit histone acetyltransferaseactivity from T cell nuclear extracts. The NH₂-terminal transactivationdomain of NFAT1 and the phospho-CREB- and E1A-binding sites ofp300/CBP are involved in the interaction. The viral oncoproteinE1A inhibits NFAT-dependent transactivation in a p300-dependentmanner. Recruitment of the coactivators p300/CBP by the transactivationdomains of NFAT proteins is likely to play a critical role inNFAT-dependent gene expression during the immune response.

Key words: transcriptional regulation; histone acetyltransferases; T cells; nuclear factor of activated T cells; cytokine gene expression

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