RGD Reference Report - Endothelin-1-dependent nuclear factor of activated T lymphocyte signaling associates with transcriptional coactivator p300 in the activation of the B cell leukemia-2 promoter in cardiac myocytes. - Rat Genome Database

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Endothelin-1-dependent nuclear factor of activated T lymphocyte signaling associates with transcriptional coactivator p300 in the activation of the B cell leukemia-2 promoter in cardiac myocytes.

Authors: Kawamura, T  Ono, K  Morimoto, T  Akao, M  Iwai-Kanai, E  Wada, H  Sowa, N  Kita, T  Hasegawa, K 
Citation: Kawamura T, etal., Circ Res. 2004 Jun 11;94(11):1492-9. Epub 2004 Apr 29.
RGD ID: 2312277
Pubmed: PMID:15117818   (View Abstract at PubMed)
DOI: DOI:10.1161/01.RES.0000129701.14494.52   (Journal Full-text)

Endothelin-1 (ET-1) is a potent survival factor that protects cardiac myocytes from apoptosis. ET-1 induces cardiac gene transcription and protein expression of antiapoptotic B cell leukemia-2 (bcl-2) in a calcineurin-dependent manner. A cellular target of adenovirus early region 1A (E1A) oncoprotein, p300 also activates bcl-2 transcription in cardiac myocytes and is required for their survival. p300 acts as a calcineurin-regulated nuclear factors of activated T lymphocytes (NFATc), downstream targets of calcineurin. In addition, the bcl-2 promoter contains multiple NFAT consensus sequences. These findings prompted us to investigate the role of NFATc in ET-1-dependent and p300-dependent bcl-2 transcription in cardiac myocytes. In primary cardiac myocytes prepared from neonatal rats, mutation of 2 NFAT sites within the bcl-2 promoter completely abolished the ET-1- and p300-induced increases in the activity of this promoter. We show here that p300 markedly potentiates the binding of NFATc1 to the bcl-2 NFAT element by interacting with NFATc1 in an E1A-dependent manner. On the other hand, stimulation of cardiac myocytes with ET-1 causes nuclear translocation of NFATc1, which interacts with p300 and increases DNA binding. Expression of E1A did not change the cardiac nuclear localization of NFATc1 but blocked its interaction with p300, DNA binding, and bcl-2 promoter activation. These findings suggest that ET-1-dependent NFATc signaling associates with p300 in the transactivation of bcl-2 gene in cardiac myocytes.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA-binding transcription factor binding  IPINfatc1 (Rattus norvegicus)2312277 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ep300  (E1A binding protein p300)

Objects referenced in this article
Gene Nfatc1 nuclear factor of activated T-cells 1 Rattus norvegicus

Additional Information