1. Mad1 Function in Cell Proliferation and Transcriptional Repression Is Antagonized by Cyclin E/CDK2.
- Author
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Rottmann, Sabine, Menkel, Annette R., Bouchard, Caroline, Mertsching, Jürgen, Loidl, Peter, Kremmer, Elisabeth, Eilers, Martin, Lüscher-Firzlaff, Ejuliane, Lilischkis, Richard, and Lüscher, Bernhard
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CYCLINS , *TRANSCRIPTION factors , *CELL proliferation , *PROTEINS , *GROWTH factors , *CELL cycle - Abstract
The transcription factors of the Myc/Max/Mad network play essential roles in the regulation of cellular behavior. Mad1 inhibits cell proliferation by recruiting an mSin3-corepressor complex that contains histone deacetylase activity. Here we demonstrate that Mad1 is a potent inhibitor of the G1 to S phase transition, a function that requires Mad1 to heterodimerize with Max and to bind to the corepressor complex. Cyclin E/CDK2, but not cyclin D and cyclin A complexes, fully restored S phase progression. In addition inhibition of colony formation and gene repression by Mad1 were also efficiently antagonized by cyclin E/CDK2. This was the result of cyclin E/CDK2 interfering with the interaction of Mad1 with HDAC1 and reducing HDAC activity. Our findings define a novel interplay between the cell cycle regulator cyclin E/CDK2 and Mad1 and its associated repressor complex and suggests an additional mechanism how cyclin E/CDK2 affects the G1 to S phase transition. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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