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.
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Center for Cancer Research, Departments of Biology and Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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D020816:Amino Acid Motifs; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004318:Doxycycline / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D050778:NFATC Transcription Factors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012694:Serine / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D019745:cis-trans-Isomerases / Q000737:chemistry*
D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009687:Nuclear Proteins; D014157:Transcription Factors; D012694:Serine; D015759:Ionomycin; D011392:Proline; D005982:Glutathione Transferase; D019703:Calcineurin; D019745:cis-trans-Isomerases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; D004318:Doxycycline; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium