NFATc2-mediated repression of cyclin-dependent kinase 4 expression

被引：153
作者：
Baksh, S
Widlund, HR
Frazer-Abel, AA
Du, JY
Fosmire, S
Fisher, DE
DeCaprio, JA
Modiano, JF
Burakoff, SJ
机构：
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA
[3] AMC Canc Res Ctr, Denver, CO 80214 USA
[4] Donald Monk Canc Res Fdn, Denver, CO 80214 USA
[5] Univ Colorado, Ctr Canc, Denver, CO 80262 USA
[6] NYU, Sch Med, Skirball Inst Biomol Med, New York, NY 10016 USA
来源：
MOLECULAR CELL | 2002年 / 10卷 / 05期
关键词：
D O I：
10.1016/S1097-2765(02)00701-3
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 Aalpha(-/-) 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.
引用
收藏
页码：1071 / 1081
页数：11
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