cAMP responsiveness of the bovine calpastatin gene promoter

Mei Cong, Darrel E. Goll, Parker B Antin

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)186-192
Number of pages7
JournalBBA - Gene Structure and Expression
Volume1443
Issue number1-2
DOIs
Publication statusPublished - Nov 26 1998

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Keywords

  • β-Adrenergic agonist
  • Calpain
  • Calpastatin
  • Cyclic AMP
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Structural Biology
  • Biophysics

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