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PMID: 8458330 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The functional versatility of CREM is determined by its modular structure.

The EMBO journal ·Vol. 12 ·No. 3 ·1993-03-00 ·Pages 1179-91

Laoide BM, Foulkes NS, Schlotter F, Sassone-Corsi P

Abstract

The CREM gene (cAMP-responsive element modulator) generates both activators and repressors of cAMP-induced transcription by alternative splicing. We determined the exon structure of the CREM gene and have identified new isoforms. We show that CREM isoforms with different structural characteristics are generated by the shuffling of exons to produce proteins with various combinations of functional domains. CREM proteins bind efficiently to CREs and here we demonstrate that the various isoforms heterodimerize in vivo with each other and with CREB. The two alternative DNA binding domains of CREM, which are differentially spliced in the various isoforms, show distinct binding efficiencies, while CREM alpha/CREB heterodimers exhibit stronger binding than CREM beta/CREB heterodimers to a consensus CRE in vitro. We identify the protein domains involved in activation function and find that the phosphorylation domain and a single glutamine-rich domain are sufficient for activation. A minimal CREM repressor, containing only the b-Zip motif, efficiently antagonizes cAMP-induced transcription. In addition, phosphorylation may reduce repressor function, as a CREM beta mutant carrying a mutation of the serine phosphoacceptor site (CREM beta 68) represses more efficiently than the wild-type CREM beta.

Related Genes
CREM
MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence Cells, Cultured Cyclic AMP Response Element Modulator DNA/metabolism DNA-Binding Proteins/chemistry,genetics,physiology Exons Gene Expression Regulation Glutamine/metabolism HeLa Cells Humans Leucine Zippers/genetics Molecular Sequence Data Phosphorylation Protein Binding Protein Kinases/metabolism Repressor Proteins
Chemicals
DNA-Binding Proteins Repressor Proteins Glutamine Cyclic AMP Response Element Modulator DNA Protein Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Laoide B M
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, U184 de l'INSERM, Faculté de Médecine, Strasbourg, France.
Foulkes N S
Schlotter F
Sassone-Corsi P
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-03-00
Pages
1179-91
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413321
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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