Interaction of calcineurin with a domain of the transcription factor NFAT1 that controls nuclear import.
The nuclear import of the nuclear factor of activated T cells (NFAT)-family transcription factors is initiated by the protein phosphatase calcineurin. Here we identify a regulatory region of NFAT1, N terminal to the DNA-binding domain, that controls nuclear import of NFAT1. The regulatory region of NFAT1 binds directly to calcineurin, is a substrate for calcineurin in vitro, and shows regulated subcellular localization identical to that of full-length NFAT1. The corresponding region of NFATc likewise binds calcineurin, suggesting that the efficient activation of NFAT1 and NFATc by calcineurin reflects a specific targeting of the phosphatase to these proteins. The presence in other NFAT-family transcription factors of several sequence motifs from the regulatory region of NFAT1, including its probable nuclear localization sequence, indicates that a conserved protein domain may control nuclear import of all NFAT proteins.
Luo
C
C
Division of Cellular and Molecular Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Shaw
K T
KT
Raghavan
A
A
Aramburu
J
J
Garcia-Cozar
F
F
Perrino
B A
BA
Hogan
P G
PG
Rao
A
A
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D002451:Cell Compartmentation; D002467:Cell Nucleus / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010446:Peptide Fragments / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; D050778:NFATC Transcription Factors; C494006:NFATC2 protein, human; D009687:Nuclear Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014157:Transcription Factors; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases