At the Cutting Edge What is a cAMP response unit?

• Published in: Molecular and cellular endocrinology Vol. 162; no. 1; pp. 1 - 7
• Main Author: Roesler, William J
• Format: Journal Article
• Language: English
• Published: Elsevier Ireland Ltd 01.04.2000
• Subjects: cAMP response element; cAMP response element binding protein; CCAAT/enhancer binding protein; Cyclic AMP; Phosphoenolpyruvate carboxykinase; Transcription; cAMP response element; Cyclic AMP; Transcription; Phosphoenolpyruvate carboxykinase; CCAAT/enhancer binding protein; cAMP response element binding protein
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/S0303-7207(00)00198-2

Phosphoenolpyruvate carboxykinase (PEPCK) is the rate-limiting enzyme of gluconeogenesis, and most, if not all, of the regulation of its activity is exerted at the level of gene expression, with transcriptional regulation being the most predominant. A number of hormones regulate transcription of this gene, but in a defined, tissue-specific fashion. For example, cAMP strongly induces PEPCK gene transcription in liver, but provides only a weak response in kidney. Results from a number of different studies indicate that cAMP responsiveness of this gene is mediated by a ‘cAMP response unit’ (CRU), consisting of five cis-elements. All five sequences are required for maximal responsiveness and, potentially, four of these are binding sites for a CCAAT/enhancer binding protein (C/EBP). Since α- and β-isoforms of C/EBP are liver-enriched, this may provide the molecular basis for the liver-specific responsiveness to cAMP. A curiosity of this promoter is that one of the cis-elements present in the CRU is a cAMP response element (CRE), which typically acts as a binding site for CRE binding protein (CREB). However, the non-consensus CRE in the PEPCK promoter also binds C/EBP proteins with high affinity, and C/EBPα can functionally substitute for CREB in this cAMP response unit while C/EBPβ cannot. The available data suggest that the PEPCK promoter can exist in altered states of cAMP responsivity, depending on which transcription factors occupy specific cis-elements in the CRU.