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IRF2BP2 is a new NFAT1 partner acting as a repressor protein
Author(s) -
Carneiro Flavia Raquel Gonçalves,
RamalhoOliveira Renata,
Mognol Giuliana P.,
AraujoSouza Patrícia S.,
Viola João P.B.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb57
Subject(s) - nfat , repressor , transactivation , transcription factor , nuclear localization sequence , biology , dna binding domain , promoter , genetics , luciferase , microbiology and biotechnology , gene , gene expression , transfection
NFAT family of transcription factors encodes 5 members and is present in a wide range of cell types, regulating genes involved in cell proliferation, angiogenesis, cell cycle progression and apoptosis. NFAT family has two well conserved regions: the regulatory domain and DNA binding domain. N and C‐terminal ends are transactivation sites and show less sequence similarity. To understand the molecular mechanisms related to NFAT functions we performed a yeast two hybrid screening using the less conserved NFAT1 C‐terminal end as bait. We identified that NFAT1 interacts with IRF2BP2 transcriptional repressor by its RING domain. This interaction seems to be NFAT1 specific, since the other conserved regions of NFAT1 do not interact with IRF2BP2. Furthermore, NFAT1 and IRF2BP2 co‐localize in the nucleus in activated cells and luciferase report assays demonstrate that IRF2BP2 represses the NFAT1‐dependent activation of IL‐2 and IL‐4 promoters and TNF‐alfa k3 element. We also identified a nuclear localization signal in IRF2BP2 and mutation of this signal abolishes the repression function of IRF2BP2. Our data demonstrated that IRF2BP2 interacts with NFAT1 and repress its transcriptional activity, suggesting that IRF2BP2 can be a new regulator of NFAT1 transcriptional activity. Financial support: CNPq, FAPERJ, ICGEB