Author/Authors :
Günter W. Klappacher، نويسنده , , Victoria V. Lunyak، نويسنده , , David B. Sykes، نويسنده , , Dominique Sawka-Verhelle، نويسنده , , Julien Sage، نويسنده , , Gyan Brard، نويسنده , , Sally D. Ngo، نويسنده , , Denise Gangadharan، نويسنده , , Tyler Jacks.، نويسنده , , Mark P. Kamps، نويسنده , , David W. Rose، نويسنده , , Michael G. Rosenfeld، نويسنده , , Christopher K. Glass، نويسنده ,
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.
