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Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation.

Publication ,  Journal Article
Loriaux, MM; Brennan, RG; Goodman, RH
Published in: J Biol Chem
November 18, 1994

The cAMP-responsive element (CRE) modulator protein CREM alpha has been proposed to be a negative regulator of the CRE-binding protein (CREB). Precisely how CREM alpha inhibits CREB function is unclear, however. CREM alpha and CREB have highly related structures, and both proteins bind to consensus CRE sequences with similar affinities. Furthermore, both proteins can be phosphorylated by cAMP-dependent protein kinase A (PKA). Two models have been proposed to explain how CREM alpha could prevent the activation of genes by PKA-phosphorylated CREB: inhibitory CREM alpha homodimers could prevent occupancy of the CRE by CREB, or CREM alpha could block gene activation by forming non-functional CREB.CREM alpha heterodimers. To determine whether CREB-CREM alpha heterodimers are indeed non-functional, we engineered the leucine zipper regions of the two proteins to direct the pattern of dimerization. We then tested the biological activities of the phosphorylated and nonphosphorylated complexes in in vivo transcription assays. Our results indicate that CREM alpha can contribute to PKA-mediated gene activation when selectively heterodimerized with CREB. Furthermore, this transcriptional activity depends upon the ability of the complexes to be phosphorylated by PKA.

Duke Scholars

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

November 18, 1994

Volume

269

Issue

46

Start / End Page

28839 / 28843

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Repressor Proteins
  • Phosphorylation
  • Oligodeoxyribonucleotides
  • Molecular Sequence Data
  • Leucine Zippers
  • DNA-Binding Proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic AMP Response Element-Binding Protein
  • Cyclic AMP Response Element Modulator
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Loriaux, M. M., Brennan, R. G., & Goodman, R. H. (1994). Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation. J Biol Chem, 269(46), 28839–28843.
Loriaux, M. M., R. G. Brennan, and R. H. Goodman. “Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation.J Biol Chem 269, no. 46 (November 18, 1994): 28839–43.
Loriaux MM, Brennan RG, Goodman RH. Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation. J Biol Chem. 1994 Nov 18;269(46):28839–43.
Loriaux, M. M., et al. “Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation.J Biol Chem, vol. 269, no. 46, Nov. 1994, pp. 28839–43.
Loriaux MM, Brennan RG, Goodman RH. Modulatory function of CREB.CREM alpha heterodimers depends upon CREM alpha phosphorylation. J Biol Chem. 1994 Nov 18;269(46):28839–28843.

Published In

J Biol Chem

ISSN

0021-9258

Publication Date

November 18, 1994

Volume

269

Issue

46

Start / End Page

28839 / 28843

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Repressor Proteins
  • Phosphorylation
  • Oligodeoxyribonucleotides
  • Molecular Sequence Data
  • Leucine Zippers
  • DNA-Binding Proteins
  • Cyclic AMP-Dependent Protein Kinases
  • Cyclic AMP Response Element-Binding Protein
  • Cyclic AMP Response Element Modulator