Open AccessNegative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation.
Author(s) -
William W. Lamph,
Varavani J. Dwarki,
Rivka Ofir,
Marc Montminy,
Inder M. Verma
Publication year - 1990
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.87.11.4320
Subject(s) - creb , creb1 , cyclic amp response element binding protein , forskolin , phosphorylation , response element , psychological repression , transcription factor , activator (genetics) , protein kinase a , microbiology and biotechnology , activating transcription factor , repressor , creb binding protein , chemistry , biology , promoter , biochemistry , receptor , gene expression , gene
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.