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An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation.

Defining the molecular mechanisms that coordinately regulate proliferation and differentiation is a central issue in development. Here, we describe a mechanism in which induction of the Ets repressor METS/PE1 links terminal differentiation to cell cycle arrest. Using macrophages as a model, we provide evidence that METS/PE1 blocks Ras-dependent proliferation without inhibiting Ras-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Antiproliferative effects of METS require its interaction with DP103, a DEAD box-containing protein that assembles a novel corepressor complex. Functional interactions between the METS/DP103 complex and E2F/ pRB family proteins are also necessary for inhibition of cellular proliferation, suggesting a combinatorial code that directs permanent cell cycle exit during terminal differentiation.

Pubmed ID: 12007404

Authors

  • Klappacher GW
  • Lunyak VV
  • Sykes DB
  • Sawka-Verhelle D
  • Sage J
  • Brard G
  • Ngo SD
  • Gangadharan D
  • Jacks T
  • Kamps MP
  • Rose DW
  • Rosenfeld MG
  • Glass CK

Journal

Cell

Publication Data

April 19, 2002

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK 54802
  • Agency: NHLBI NIH HHS, Id: HL 59694

Mesh Terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Division
  • Cells, Cultured
  • DEAD Box Protein 20
  • DEAD-box RNA Helicases
  • Fungal Proteins
  • Genes, cdc
  • Guinea Pigs
  • Immune System
  • Macrophages
  • Molecular Sequence Data
  • Nuclear Proteins
  • Phosphoproteins
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • Proteins
  • RNA Helicases
  • Rats
  • Repressor Proteins
  • Retinoblastoma-Like Protein p107
  • Retinoblastoma-Like Protein p130
  • Serine Endopeptidases
  • Signal Transduction
  • Transcription Factors
  • ras Proteins