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Murine METS Protein Signaling

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The macrophage differentiation system in mouse establishes the fact that, the macrophages stop proliferate during the process of cell differentiation. Induction of METS (Mitogenic Ets Transcriptional Suppressor METS) otherwise known as Ets (E26 Avian Leukemia Oncogene) repressor, leads to terminal differentiation and cell cycle arrest. Inside macrophages, METS blocks HRas1 (Harvey Rat Sarcoma Virus Oncogene-1)-dependent proliferation without inhibiting HRas1-dependent expression of cell type-specific genes by selectively replacing Ets activators on the promoters of cell cycle control genes. Anti-proliferative effects of METS require its interaction with Ddx20 (DEAD (Asp-Glu-Ala-Asp) Box Polypeptide-20) that assembles a novel co-repressor complex (Ref.1 & 2). The transcriptional repression involving METS with Ddx20 is selective and does not involve all Ets regulated genes. While cell cycle genes are repressed [...]


1.An induced Ets repressor complex regulates growth arrest during terminal macrophage differentiation.
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.
Cell. 2002 Apr 19;109(2):169-80.
2.Differential utilization of Ras signaling pathways by macrophage colony-stimulating factor (CSF) and granulocyte-macrophage CSF receptors during macrophage differentiation.
Guidez F, Li AC, Horvai A, Welch JS, Glass CK.
Mol. Cell Biol. 1998 Jul; 18(7):3851-61.
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