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PMID:12007404
| Citation |
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 and Glass, CK (2002) An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation. Cell 109:169-80 |
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| Abstract |
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. |
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| Keywords |
Animals; Base Sequence/genetics; Binding Sites/genetics; Cell Cycle Proteins/genetics; Cell Differentiation/genetics; Cell Division/genetics; Cells, Cultured; DEAD Box Protein 20; DEAD-box RNA Helicases; Fungal Proteins; Genes, cdc/physiology; Guinea Pigs; Immune System/growth & development; Immune System/metabolism; Macrophages/metabolism; Molecular Sequence Data; Nuclear Proteins/deficiency; Nuclear Proteins/genetics; Phosphoproteins/deficiency; Phosphoproteins/genetics; Promoter Regions, Genetic/genetics; Protein Structure, Tertiary/genetics; Proteins; RNA Helicases/genetics; Rats; Repressor Proteins/genetics; Retinoblastoma-Like Protein p107; Retinoblastoma-Like Protein p130; Serine Endopeptidases/deficiency; Serine Endopeptidases/genetics; Signal Transduction/genetics; Transcription Factors; ras Proteins/genetics |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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