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PMID: 8404858 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Multiple and cooperative phosphorylation events regulate the CREM activator function.

The EMBO journal ·Vol. 12 ·No. 10 ·1993-10-00 ·Pages 3903-11

de Groot RP, den Hertog J, Vandenheede JR, Goris J, Sassone-Corsi P

Abstract

Phosphorylation is one of the major mechanisms by which the activity of transcription factors can be regulated. We have investigated the role of phosphorylation in the regulation of the transcription factor CREM. We show that the CREM tau activator is phosphorylated on multiple serine and threonine residues in vivo. Stimulation of various signal transduction pathways by forskolin, TPA or Ca2+ ionophore leads to enhanced phosphorylation of serine 117, concomitant with an increase in the transactivation potential of CREM tau. We have identified multiple kinases that can also phosphorylate S117 in vitro. Moreover, we show that casein kinase I and II cooperatively phosphorylate CREM tau on multiple residues, eliciting enhanced DNA binding. Cooperative phosphorylation is also observed with other kinases. These results show that the activity of CREM tau is regulated by multiple phosphorylation events, suggesting that CREM could be considered as a nuclear effector where signalling pathways may converge and/or cross-talk.

MeSH Terms
3T3 Cells Amino Acid Sequence Animals Base Sequence Cell Line Cyclic AMP Response Element Modulator DNA DNA-Binding Proteins/metabolism Mice Molecular Sequence Data Peptide Mapping Phosphorylation Protein Kinases/metabolism Repressor Proteins Signal Transduction Transcription Factors/metabolism Transcriptional Activation
Chemicals
DNA-Binding Proteins Repressor Proteins Transcription Factors Cyclic AMP Response Element Modulator DNA Protein Kinases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
de Groot R P
Laboratoire Génétique Moléculaire des Eucaryotes, CNRS, U184 de l'INSERM, Faculté de Médecine, Institut de Chimie Biologique, Strasbourg, France.
den Hertog J
Vandenheede J R
Goris J
Sassone-Corsi P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-10-00
Pages
3903-11
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413673
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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