NFATc2-mediated repression of cyclin-dependent kinase 4 expression
- PMID: 12453415
- DOI: 10.1016/s1097-2765(02)00701-3
NFATc2-mediated repression of cyclin-dependent kinase 4 expression
Abstract
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.
Similar articles
-
Nuclear factor of activated T cells and serum response factor cooperatively regulate the activity of an alpha-actin intronic enhancer.J Biol Chem. 2005 Jul 15;280(28):26113-20. doi: 10.1074/jbc.M411972200. Epub 2005 Apr 27. J Biol Chem. 2005. PMID: 15857835
-
c-Jun N-terminal kinase (JNK) positively regulates NFATc2 transactivation through phosphorylation within the N-terminal regulatory domain.J Biol Chem. 2005 May 27;280(21):20867-78. doi: 10.1074/jbc.M501898200. Epub 2005 Mar 2. J Biol Chem. 2005. PMID: 15743762
-
Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis.EMBO J. 2000 Aug 15;19(16):4323-31. doi: 10.1093/emboj/19.16.4323. EMBO J. 2000. PMID: 10944115 Free PMC article.
-
Regulation of MAPK signaling pathways through immunophilin-ligand complex.Curr Top Med Chem. 2003;3(12):1358-67. doi: 10.2174/1568026033451916. Curr Top Med Chem. 2003. PMID: 12871167 Review.
-
Inhibitors of the calcineurin/NFAT pathway.Curr Med Chem. 2004 Apr;11(8):997-1007. doi: 10.2174/0929867043455576. Curr Med Chem. 2004. PMID: 15078162 Review.
Cited by
-
Impact of natural genetic variation on gene expression dynamics.PLoS Genet. 2013 Jun;9(6):e1003514. doi: 10.1371/journal.pgen.1003514. Epub 2013 Jun 6. PLoS Genet. 2013. PMID: 23754949 Free PMC article.
-
Transgenic overexpression of active calcineurin in beta-cells results in decreased beta-cell mass and hyperglycemia.PLoS One. 2010 Aug 3;5(8):e11969. doi: 10.1371/journal.pone.0011969. PLoS One. 2010. PMID: 20689817 Free PMC article.
-
Requirement for balanced Ca/NFAT signaling in hematopoietic and embryonic development.Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):7034-9. doi: 10.1073/pnas.0813296106. Epub 2009 Apr 7. Proc Natl Acad Sci U S A. 2009. PMID: 19351896 Free PMC article.
-
Transcription factor ELF4 controls the proliferation and homing of CD8+ T cells via the Krüppel-like factors KLF4 and KLF2.Nat Immunol. 2009 Jun;10(6):618-26. doi: 10.1038/ni.1730. Epub 2009 May 3. Nat Immunol. 2009. PMID: 19412182 Free PMC article.
-
Transcription factor NFAT1 controls allergic contact hypersensitivity through regulation of activation induced cell death program.Sci Rep. 2016 Jan 18;6:19453. doi: 10.1038/srep19453. Sci Rep. 2016. PMID: 26777750 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Research Materials
