DREAM-alphaCREM interaction via leucine-charged domains derepresses downstream regulatory element-dependent transcription

Mol Cell Biol. 2000 Dec;20(24):9120-6. doi: 10.1128/MCB.20.24.9120-9126.2000.

Abstract

Protein kinase A-dependent derepression of the human prodynorphin gene is regulated by the differential occupancy of the Dyn downstream regulatory element (DRE) site. Here, we show that a direct protein-protein interaction between DREAM and the CREM repressor isoform, alphaCREM, prevents binding of DREAM to the DRE and suggests a mechanism for cyclic AMP-dependent derepression of the prodynorphin gene in human neuroblastoma cells. Phosphorylation in the kinase-inducible domain of alphaCREM is not required for the interaction, but phospho-alphaCREM shows higher affinity for DREAM. The interaction with alphaCREM is independent of the Ca(2+)-binding properties of DREAM and is governed by leucine-charged residue-rich domains located in both alphaCREM and DREAM. Thus, our results propose a new mechanism for DREAM-mediated derepression that can operate independently of changes in nuclear Ca(2+).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / genetics*
  • Amino Acid Sequence
  • Calcium / metabolism
  • Calcium-Binding Proteins*
  • Cell Line
  • Colforsin / pharmacology
  • Cyclic AMP Response Element Modulator
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enkephalins / drug effects
  • Enkephalins / genetics*
  • Gene Expression Regulation / drug effects
  • Genes, Regulator / genetics*
  • Genes, Reporter / genetics
  • Humans
  • Kv Channel-Interacting Proteins
  • Molecular Sequence Data
  • Mutation / genetics
  • Neuroblastoma
  • Phosphorylation
  • Protein Precursors / drug effects
  • Protein Precursors / genetics*
  • RNA, Messenger / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins / chemistry
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Sequence Alignment
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Calcium-Binding Proteins
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Enkephalins
  • KCNIP3 protein, human
  • Kv Channel-Interacting Proteins
  • Protein Precursors
  • RNA, Messenger
  • Recombinant Proteins
  • Repressor Proteins
  • Cyclic AMP Response Element Modulator
  • Colforsin
  • preproenkephalin
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium