NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun.
NFAT transcription factors are related to NF-kappaB/Rel proteins and form cooperative complexes with Fos and Jun on DNA. We have identified an NFAT-related protein, NFAT5, which differs from the conventional NFAT proteins NFAT1-4 in its structure, DNA binding, and regulation. NFAT5 contains a NFAT-like Rel homology domain, conserves the DNA contact residues of NFAT1-4, and binds DNA sequences similar to those found in the regulatory regions of well-characterized NFAT-dependent genes. However, it lacks the majority of Fos/Jun contact residues and does not bind cooperatively with Fos and Jun to DNA. Unlike NFAT1-4, whose nuclear import is tightly regulated by calcineurin-mediated dephosphorylation, NFAT5 is a constitutively nuclear phosphoprotein regardless of calcineurin activation. These features suggest that unlike the conventional NFAT proteins, NFAT1-4, which activate gene transcription by integrating inputs from calcium/calcineurin and protein kinase C/mitogen-activated protein kinase signaling pathways, NFAT5 participates in as-yet-unidentified signaling pathways in diverse immune and nonimmune cells.
Lopez-Rodríguez
C
C
Department of Pathology, Harvard Medical School, The Center for Blood Research, Boston, MA 02115, USA.
Aramburu
J
J
Rakeman
A S
AS
Rao
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002461:Cell Line, Transformed; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors