Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation

W. W. Lamph, V. J. Dwarki, R. Ofir, M. Montminy, I. M. Verma

Research output: Contribution to journalArticlepeer-review

182 Scopus citations

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 phoshorylation 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.

Original languageEnglish
Pages (from-to)4320-4324
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number11
DOIs
StatePublished - 20 Jul 1990
Externally publishedYes

Keywords

  • AP-1
  • c-Fos protein
  • c-Jun protein
  • protein kinase A
  • transrepression

Fingerprint

Dive into the research topics of 'Negative and positive regulation by transcription factor cAMP response element-binding protein is modulated by phosphorylation'. Together they form a unique fingerprint.

Cite this