Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation.
Year: 1990
Type: article
Abstract: We have shown that the transcriptional activity of the protooncogene jun (c-jun) promoter is repressed by a transcription factor, the cAMP response element-binding protein (CREB). This repression can be alleviated when CREB is phosphorylated by the catalytic subunit of protein kinase A. Repression cannot be alleviated by a mutant CREB deficient in the protein kinase A phosphorylation site (M1 CREB Ser-133----Ala), suggesting that phosphorylation of CREB at this site is essential for the relief of repression. Repression by CREB requires its binding to the c-jun promoter. In NIH 3T3 cells stably expressing CREB, c-jun is no longer induced by serum, but this repression can be relieved by treatment of the cells with forskolin, an agonist of the adenylate cyclase pathway. Thus, CREB has a dual function, that of a repressor in the absence of phosphorylation and an activator when phosphorylated by protein kinase A.
Authors: W W Lamph, V J Dwarki, R Ofir, M Montminy, I M Verma
Institution: Salk Institute for Biological Studies
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1980854045