NFATc2-mediated repression of cyclin-dependent kinase 4 expression

Shairaz Baksh, Hans R. Widlund, Ashley A. Frazer-Abel, Jinyan Du, Susan Fosmire, David E. Fisher, James A. DeCaprio, Jaime F. Modiano, Steven J. Burakoff

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


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.

Original languageEnglish
Pages (from-to)1071-1081
Number of pages11
JournalMolecular Cell
Issue number5
StatePublished - 1 Nov 2002
Externally publishedYes


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