| pubmed-article:20371871 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0330390 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0054450 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0815047 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0597716 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C2587213 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C2911684 | lld:lifeskim |
| pubmed-article:20371871 | lifeskim:mentions | umls-concept:C0185117 | lld:lifeskim |
| pubmed-article:20371871 | pubmed:issue | 22 | lld:pubmed |
| pubmed-article:20371871 | pubmed:dateCreated | 2010-5-24 | lld:pubmed |
| pubmed-article:20371871 | pubmed:abstractText | Regulator of calcineurin 1 (RCAN1) inhibits the protein phosphatase calcineurin and is required for appropriate immune responses, synaptic plasticity, vascular tone, angiogenesis, and cardiac remodeling. Expression of the RCAN1-4 isoform is under the control of the calcineurin-responsive transcription factor NFAT. Typically, NFATs act in cooperation with other transcription factors to achieve maximal activation of gene expression. In this study, we identify the CCAAT/enhancer binding protein beta (C/EBPbeta) as an NFAT binding partner that cooperates with NFAT to regulate RCAN1-4 expression. Numerous C/EBPbeta binding sites are conserved in the RCAN1-4 proximal promoter. Overexpression of C/EBPbeta increased activity of both the endogenous mouse Rcan1-4 gene and a human RCAN1-4 luciferase reporter. Binding of C/EBPbeta to multiple sites in the promoter was verified using electrophoretic mobility shift assays and chromatin immunoprecipitation. A direct interaction between C/EBPbeta and NFAT was demonstrated by co-immunoprecipitation of proteins and complex formation at NFAT-C/EBPbeta composite sites. Depletion of endogenous C/EBPbeta decreased maximal activation of RCAN1-4 expression by calcineurin, whereas inhibition of calcineurin did not alter the ability of C/EBPbeta to activate RCAN1-4 expression. Together, these findings suggest that calcineurin/NFAT activation of RCAN1-4 expression is in part dependent upon C/EBPbeta, whereas activation by C/EBPbeta is not dependent on calcineurin and may provide a calcineurin-independent pathway for regulating RCAN1-4 expression. Importantly, nuclear localization, C/EBPbeta DNA binding activity and occupancy of the Rcan1-4 promoter increased in mouse models of heart failure demonstrating in vivo activation of this pathway to regulate Rcan1-4 expression and ultimately shape the dynamics of calcineurin-dependent signaling. | lld:pubmed |
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| pubmed-article:20371871 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20371871 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20371871 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20371871 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:20371871 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20371871 | pubmed:month | May | lld:pubmed |
| pubmed-article:20371871 | pubmed:issn | 1083-351X | lld:pubmed |
| pubmed-article:20371871 | pubmed:author | pubmed-author:HillJoseph... | lld:pubmed |
| pubmed-article:20371871 | pubmed:author | pubmed-author:GerardRobert... | lld:pubmed |
| pubmed-article:20371871 | pubmed:author | pubmed-author:RothermelBeve... | lld:pubmed |
| pubmed-article:20371871 | pubmed:author | pubmed-author:OhMisookM | lld:pubmed |
| pubmed-article:20371871 | pubmed:author | pubmed-author:DeyAsimA | lld:pubmed |
| pubmed-article:20371871 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20371871 | pubmed:day | 28 | lld:pubmed |
| pubmed-article:20371871 | pubmed:volume | 285 | lld:pubmed |
| pubmed-article:20371871 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20371871 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20371871 | pubmed:pagination | 16623-31 | lld:pubmed |
| pubmed-article:20371871 | pubmed:dateRevised | 2011-7-28 | lld:pubmed |
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| pubmed-article:20371871 | pubmed:year | 2010 | lld:pubmed |
