Details

Autor(en) / Beteiligte

• Montminy, M.
• Brindle, P.
• Arias, J.
• Ferreri, K.
• Armstrong, R.

Titel

Regulation of Somatostatin Gene Transcription by cAMP

Ist Teil von

• Advances in Pharmacology, 1996, Vol.36, p.1-13

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

1996

Quelle

MEDLINE

Beschreibungen/Notizen

• Characterized by a core motif, which often contains the palindromic sequence 5’-TGACGTCA-3’, the CRE can confer cAMP inducibility when placed upstream of a heterologous promoter and can function in both distance- and orientation-independent contexts. Remarkably, mutant cell lines deficient in PKA cannot support CAMP- responsive transcription from a CRE reporter gene, suggesting that this kinase might phosphorylate proteins that bind to the CRE and, thereby activate transcription of cAMP-responsive genes. Previous work showing that most, if not all, of the biological effects of cAMP are mediated by the CAMP-dependent PKA prompted researchers to test whether CREB activity in response to cAMP might be dependent on phosphorylation by PKA. Like other signaling pathways, cAMP stimulates transcription of somatostatin and other target genes with burst-attenuation kinetics: transcription usually peaks within 20-30 min of induction and gradually declines over the next 4-8 hr. The second phase in CAMP-responsive transcription is an attenuation phase during which CREB phosphorylation and CRE-dependent transcription decrease in parallel over a 4-hr period. During that time, levels of total CREB protein remain unchanged, suggesting that a CREB phosphatase may be critical in down-regulating CAMP-induced transcription. The kinetics of PKA-dependent CREB phosphorylation closely parallel the changes in transcription of CAMP-responsiveness by run-on assay.