NFATc2-Mediated Repression of Cyclin-Dependent Kinase 4 Expression

• Autores: Shairaz Baksh, H. R. Widlund, A. A. Frazer-abel
• Localización: Molecular cell, ISSN 1097-2765, Nº 10, 2002, págs. 1071-1082
• Idioma: inglés
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• Resumen

  • The calcineurin-regulated transcription factor, nuclear factor of activated T cells (NFAT), controls many aspects of T cell function. Here, we demonstrate that the calcineurin/NFAT pathway negatively regulates the expression of cyclin-dependent kinase 4 (CDK4). A canonical NFAT binding site was identified and found to be sensitive to calcium signals, FK506/CsA, and histone deacetylase activity and to not require AP-1. Ectopic expression of NFATc2 inhibited the basal activity of the human CDK4 promoter. Additionally, both calcineurin Aα−/− and NFATc2−/− mice had elevated protein levels of CDK4, confirming a negative regulatory role for the calcineurin/NFAT pathway. This pathway may thus regulate the expression of CDK4 at the transcriptional level and control how cells re-enter a resting, nonproliferative state.