Pineal Transcription Factors and Their Possible Roles for the Regulation of the Melatonin Biosynthesis

Abstract

In recent years considerable progress has been made toward identifying pineal transcription factors and their possible role for the control of melatonin biosynthesis. These studies (nearly all of them performed with mammals) have highlighted the importance of transcription factors that are controlled by the NE/cAMP pathway and impinge on genes bearing a promoter element sensitive to elevation of intracellular cAMP levels (CRE, see below). An essential component of this transmembrane signaling pathway is the cAMP-inducible protein kinase A (PKA). This enzyme consists of catalytic and regulatory subunits (see Maronde et al. 1997a) which are aggregated under resting conditions but dissociate upon cAMP elevation. The catalytic subunits of the PKA phosphorylate constitutively expressed proteins in the cytoplasm and/or - upon translocation into the nucleus - nuclear proteins, as transcription factors. Transcription factors can bind to promotor and enhancer sequences located on genes upstream of the start site of DNA transcription to modulate the activity of DNA polymerases. This leads to an activation or inhibition of DNA transcription and constitutes a fundamental link between an external cue and an adaptive cellular response to appropriately react in time and space.