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.
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
Cell
Date: Apr. 19, 2002
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