Binding and regulation of the transcription factor NFAT by the peptidyl prolyl cis-trans isomerase Pin1.
Nuclear factor of activated T cells (NFAT) plays a key role in T cell activation. The activation of NFAT involves calcium- and calcineurin-dependent dephosphorylation and nuclear translocation from the cytoplasm, a process that is opposed by protein kinases. We show here that the peptidyl prolyl cis-trans isomerase Pin1 interacts specifically ... with the phosphorylated form of NFAT. The NFAT-Pin1 interaction is mediated through the WW domain of Pin1 and the serine-proline-rich domains of NFAT. Furthermore, binding of Pin1 to NFAT inhibits the calcineurin-mediated dephosphorylation of NFAT in vitro, and overexpression of Pin1 in T cells inhibits calcium-dependent activation of NFAT in vivo. These results suggest a possible role for Pin1 in the regulation of NFAT in T cells.
Mesh Terms:
Amino Acid Motifs, Blotting, Western, Calcineurin, Calcium, DNA-Binding Proteins, Doxycycline, Glutathione Transferase, Humans, Ionomycin, Jurkat Cells, Lymphocyte Activation, NFATC Transcription Factors, Nuclear Proteins, Peptidylprolyl Isomerase, Phosphorylation, Plasmids, Proline, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Serine, Tetradecanoylphorbol Acetate, Transcription Factors, Transcription, Genetic, Transfection, cis-trans-Isomerases
Amino Acid Motifs, Blotting, Western, Calcineurin, Calcium, DNA-Binding Proteins, Doxycycline, Glutathione Transferase, Humans, Ionomycin, Jurkat Cells, Lymphocyte Activation, NFATC Transcription Factors, Nuclear Proteins, Peptidylprolyl Isomerase, Phosphorylation, Plasmids, Proline, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Serine, Tetradecanoylphorbol Acetate, Transcription Factors, Transcription, Genetic, Transfection, cis-trans-Isomerases
FEBS Lett.
Date: May. 11, 2001
PubMed ID: 11356192
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