Take your "M" time

Abstract

Both entry and exit from mitosis are driven through the fine modulation of Cdk1 activity by several proteins or protein complexes. It is well established that to enter into the M-phase a cell requires Cdk1 to be fully activated in the nucleus by the Cdc25A, B and C phosphatases. Then, at the onset of anaphase Cdk1 activity suddenly drops mainly due to Cyclin B1 degradation, thus allowing exit from M-phase. Recent data demonstrate that high Cdk1 activity is necessary also for proper chromosome segregation, since its premature drop determines acceleration of the progression from prophase to metaphase eventually with incorrect division of the DNA content. A primary role in maintaining high Cdk1 activity during prophase and metaphase is played by Cdc25C phosphatase. During the M-phase, the activity of Cdc25C is regulated by the FEZ1/LZTS1 (LZTS1) tumor suppressor gene, which is able to prevent Cdc25C degradation in mitotic cells. As a consequence, Lzts1 absence in mice results in accelerated mitotic progression, improper chromosome segregation and, eventually, in increased incidence of both spontaneous and carcinogen-induced cancer formation. © 2007 Landes Bioscience.