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Mad1 Function in Cell Proliferation and Transcriptional Repression Is Antagonized by Cyclin E/CDK2.

Authors :
Rottmann, Sabine
Menkel, Annette R.
Bouchard, Caroline
Mertsching, Jürgen
Loidl, Peter
Kremmer, Elisabeth
Eilers, Martin
Lüscher-Firzlaff, Ejuliane
Lilischkis, Richard
Lüscher, Bernhard
Source :
Journal of Biological Chemistry. 4/22/2005, Vol. 280 Issue 16, p15489-15492. 4p. 9 Graphs.
Publication Year :
2005

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]

Details

Language :
English
ISSN :
00219258
Volume :
280
Issue :
16
Database :
Academic Search Index
Journal :
Journal of Biological Chemistry
Publication Type :
Academic Journal
Accession number :
16951915
Full Text :
https://doi.org/10.1074/jbc.C400611200