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  current news   Press   selected story    
     
  15th December  
 

Cdc25A serine 123 phosphorylation couples centrosome duplication with DNA replication and regulates tumorigenesis.

 
 




Authors
Shreeram S, Hee WK and Bulavin DV.

Abstract
The cell division cycle 25A (Cdc25A) phosphatase is a critical regulator of cell cycle progression under normal conditions and after stress. Stress-induced degradation of Cdc25A has been proposed as a major way of delaying cell cycle progression. In vitro studies pointed towards serine 123 as a key site in regulation of Cdc25A stability after exposure to ionizing radiation (IR). To address the role of this phosphorylation site in vivo, we generated a knock-in mouse in which serine 123 was substituted for alanine. The Cdc25 Ser123A knock-in mice appeared normal, and, unexpectedly, cells derived from them exhibited unperturbed cell cycle and DNA damage responses. In turn, we found that Cdc25A was present in centrosomes and that Cdc25A levels were not reduced after IR in knock-in cells. This resulted in centrosome amplification due to lack of induction of Cdk2 inhibitory phosphorylation after IR specifically in centrosomes. Further, Cdc25A knock-in animals appeared sensitive to IR-induced carcinogenesis. Our findings indicate that Cdc25A Ser123 phosphorylation is crucial for coupling centrosome duplication to DNA replication cycles after DNA damage, and therefore is likely to play a role in the regulation of tumorigenesis.

 
 


 
 


Published in Mol Cell Biol. 2008 Dec; 28(24):7442-50

For more information on Dmitry BULAVIN ’s Lab, Please Click here.