Open AccessA dimer-specific function of the transcription factor NFATp
Author(s) -
James V. Falvo,
Charles Lin,
Alla V. Tsytsykova,
Peter K. Hwang,
Dimitris Thanos,
Anne E. Goldfeld,
Tom Maniatis
Publication year - 2008
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0810648105
Subject(s) - nfat , bzip domain , transcription factor , dimer , leucine zipper , basic helix loop helix leucine zipper transcription factors , coactivator , activating transcription factor , transcription (linguistics) , creb , biology , dna binding domain , dna binding protein , microbiology and biotechnology , genetics , gene , chemistry , linguistics , philosophy , organic chemistry
The transcription factor NFATp integrates multiple signal transduction pathways through coordinate binding with basic-region leucine zipper (bZIP) proteins and other transcription factors. The NFATp monomer, even in the absence of its activation domains, recruits bZIP proteins to canonical NFAT–bZIP composite DNA elements. By contrast, the NFATp dimer and its bZIP partner bind noncooperatively to the NFAT–bZIP element of the tumor necrosis factor (TNF ) gene promoter. This observation raises the possibility that the function of the activation domains of NFATp is dimer-specific. Here, we determine the consensus DNA binding site of the NFATp dimer, describe monomer- and dimer-specific NFATp–DNA contact patterns, and demonstrate that NFATp dimerization and dimer-specific activation subdomains are required for transcriptional activation from theTNF NFAT–bZIP element. We also show that these NFATp subdomains interact with the coactivator CBP (CREB-binding protein), which is required for NFATp-dependentTNF gene transcription. Thus, the context-specific function of the activation domains of NFAT can be potentiated by DNA-directed dimerization.