CCAAT/enhancer binding proteins: do they possess intrinsic cAMP-inducible activity?

CCAAT/enhancer binding proteins (C/EBPs) are transcription factors that are enriched in tissues which play a central role in energy metabolism, such as adipose and liver. Structure/function analyses of these proteins have identified several transactivation domains, some of which can physically interact with general transcription factors present in the preinitiation complex. C/EBPs are generally considered to be constitutively-acting factors, unlike other transcription factors whose activities can be regulated by covalent modification, binding of a specific ligand, etc. However, studies of the regulatory property of the phosphoenolpyruvate carboxykinase gene promoter have uncovered a role for C/EBPs in mediating cAMP responsiveness, and identified specific domains within the proteins, which mediate this effect. Interestingly, a number of other gene promoters that are activated in response to cAMP also contain binding sites for C/EBP, and these binding sites are often located within the region of the promoter that is responsible for mediating the acute responsiveness to cAMP. The evidence presented in this review provides compelling support for the hypothesis that C/EBPs have both constitutive and cAMP-inducible activities, and should be considered as a cAMP-responsive nuclear regulator.