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Identification and expression of a novel isoform of cAMP response element modulator in the human heart
Author(s) -
Müller Frank U.,
Bokník Peter,
Knapp Jörg,
Neumann Joachim,
Vahlensieck Ute,
Oetjen Elke,
Scheld Hans H.,
Schmitz Wilhelm
Publication year - 1998
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.12.12.1191
Subject(s) - creb , biology , creb1 , gene isoform , microbiology and biotechnology , response element , transcription (linguistics) , transcription factor , gene expression , gene , messenger rna , regulation of gene expression , creb binding protein , promoter , genetics , linguistics , philosophy
In end‐stage human heart failure, excessive β‐adrenergic stimulation of the cAMP‐dependent signaling pathway due to enhanced endogenous catecholamines is hypothesized to contribute to expressional alterations of myocardial regulatory proteins. The cAMP response element modulator (CREM) regulates the transcription of cAMP‐responsive genes and might be involved in the regulation of cardiac gene expression. Using the reverse transcription polymerase chain reaction, we identified a novel CREM mRNA, CREM‐IbδC‐X, in the human heart. Overexpression of CREM‐IbδC‐X decreased cAMP response element (CRE) ‐mediated gene transcription in HIT‐T15 cells, and this activity was assigned to the part of the sequence encoding putative internally translated proteins. Two of three possible internally translated proteins were immunologically identified in cells overexpressing CREM‐IbδC‐X tagged with the hemagglutinin epitope of the influenza virus. Both proteins were expressed in bacteria and showed CRE‐specific DNA binding, formation of heterodimers with the cAMP response element binding protein (CREB), and inhibition of CREB's binding to the CRE. CREM expression was detected on the mRNA and protein levels in the human heart. We conclude that CREM‐IbδC‐X generates internally translated repressors of CRE‐mediated gene transcription, suggesting the first example for the existence and function of human cardiac CREM.—Müller, F. U., BoknÍK, P., Knapp, Jörg, Neumann, J., Vahlensieck, U., Oetjen, E., Scheld, H. H., Schmitz, W. Identification and expression of a novel isoform of cAMP response element modulator in the human heart. FASEB J. 12, 1191–1199 (1998)