cAMP responsiveness of the bovine calpastatin gene promoter.
Biochim Biophys Acta
; 1443(1-2): 186-92, 1998 Nov 26.
Article
em En
| MEDLINE
| ID: mdl-9838106
ABSTRACT
Previous studies have shown that transcription of the gene encoding bovine calpastatin, an inhibitor of the calcium-activated cysteine protease calpain, is upregulated following activation of cAMP-dependent signaling pathways. In this study, deletion and site-directed mutagenesis experiments were performed to identify cis elements conferring cAMP responsiveness. Heterologous promoter assays demonstrated that all cAMP-responsive cis elements were located within -102 nucleotides (nt) of transcription initiation. Deletion of an element (GTCA) at nt +13 that is identical to half of the palindromic cAMP-responsive element (TGACGTCA) identified in other cAMP-responsive gene promoters had no effect on the response of the calpastatin promoter to dibutyryl-cAMP, although a 67% reduction in basal promoter activity was observed. In contrast, two point mutations in a cis element at nt -76 (GTCA to aTCt) abolished cAMP responsiveness. These results demonstrate that the calpastatin promoter sequence between nt -1653 and +130 contains a single cAMP-responsive element (GTCA) located at nt -76, and suggest a direct molecular pathway by which activation of cAMP signaling could lead to increased calpastatin gene transcription and reduction in calpain-mediated proteolysis.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Ligação ao Cálcio
/
Regiões Promotoras Genéticas
/
AMP Cíclico
Limite:
Animals
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos