Requirement of two NFATc4 transactivation domains for CBP potentiation.
Recruitment of the coactivator CREB-binding protein (CBP) to transcription factors is important for gene expression. Various regions of CBP such as the KIX and CH3 domains have been shown to interact with numerous transcription factors. The NFAT group of transcription factors is involved in multiple biological processes. NFATc4/NFAT3 has been proposed to play an important role in heart hypertrophy, adipocyte differentiation, and learning and memory. We demonstrate here that two transactivation domains, located at the NH(2) and COOH termini of NFATc4, are critical for interacting with CBP. Each transactivation domain interacts with a distinct region of the CBP protein (the KIX and CH3 domains). Binding of CBP potentiates NFATc4-mediated transcription activity. Both transactivation domains of NFATc4 are required for CBP function. Removal of either NFATc4 transactivation domain abolishes CBP potentiation. Conversely, mutation of the KIX or CH3 domain prevents CBP-mediated potentiation of NFATc4 transcription activation. These data demonstrate that formation of a functional NFATc4.CBP transcription complex requires interactions at two distinct sites.
Yang
T
T
Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461, USA.
Davis
R J
RJ
Chow
C W
CW
D001665:Binding Sites; D050882:CREB-Binding Protein; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494010:NFATC4 protein, human; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D050882:CREB-Binding Protein