CREB represses transcription of fos promoter: role of phosphorylation.

We have studied the regulation of protooncogene fos following serum induction. We show that un- or hypo-phosphorylated form of transcription factor cyclic AMP response element binding (CREB) protein represses the transcription of fos promoter. The negative regulation by CREB is alleviated if it is phosphorylated at serine 133 by the catalytic subunit of protein kinase A (PKA). A DNA binding mutant of CREB is unable to suppress transcription of the fos promoter. However, mutation in the cyclic AMP responsive element (CRE) at -60 or AP-1 binding site at -290, known to bind to CREB, does not appear to be involved in repression. Serum induction of dyad symmetry element (DSE) linked reporter gene is also repressed by unmodified CREB, which can be relieved following phosphorylation by PKA. We propose that posttranslational modification of CREB regulates serum inducibility of fos promoter.