CAMP-Dependent Regulation of Gene Transcription by cAMP Response Element-Binding Protein and cAMP Response Element Modulator

Abstract

Publisher Summary This chapter discusses cyclic AMP (cAMP)-dependent regulation of gene transcription by cAMP response element-binding protein and cAMP response element modulator. The cAMP signaling pathway is one of the most important intracellular signal transduction pathways in eukaryotic cells. In the absence of cAMP, the inactive protein kinase A (PKA) holoenzyme is a heterotetrameric protein complex consisting of two regulatory subunits (R) and two catalytic subunits (C). Two classes of R subunits, each with two isoforms, and three isoforms of the C subunits are described in the chapter. cAMP binds cooperatively to two sites on the R subunits within the holoenzyme, thereby liberating free active C subunits. Regulation of gene transcription is accomplished by the interaction of DNA-binding proteins with DNA regulatory sequences and with proteins of the general transcription machinery. Variant cAMP response elements (CREs) include asymmetrical or atypical sequences that differ from the consensus motif by single or multiple nucleotide deletions or substitutions. It is found that the interplay between the phosphorylating protein kinases and the dephosphorylating protein phosphatases is critical in determining the relative transactivation potential at any given moment.