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CBP-independent activation of CREM and CREB by the LIM-only protein ACT.

Transcriptional activation by CREB and CREM requires phosphorylation of a serine residue within the activation domain (Ser 133 in CREB; Ser 117 in CREM) which as a result interacts with the coactivator CBP. The activator CREM is highly expressed in male germ cells and is required for post-meiotic gene expression. Using a two-hybrid screen, we have isolated a testis-derived complementary DNA encoding a protein that we term ACT (for activator of CREM in testis), a LIM-only protein which specifically associates with CREM. ACT is expressed coordinately with CREM in a tissue- and developmentally regulated manner. It strongly stimulates CREM transcriptional activity in yeast and mammalian cells and contains an intrinsic activation function. As ACT bypasses the classical requirements for activation, namely phosphorylation of Ser 117 and interaction with CBP, it represents a new route for transcriptional activation by CREM and CREB. ACT may define a previously undiscovered class of tissue-specific coactivators whose function could be specific for distinct cellular differentiation programmes.

Pubmed ID: 10086359

Authors

  • Fimia GM
  • De Cesare D
  • Sassone-Corsi P

Journal

Nature

Publication Data

March 11, 1999

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • COS Cells
  • CREB-Binding Protein
  • Cyclic AMP Response Element Modulator
  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • LIM Domain Proteins
  • Male
  • Mice
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphorylation
  • Protein Binding
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Serine
  • Testis
  • Trans-Activators
  • Transcription Factors
  • Yeasts
  • Zinc Fingers