Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1.
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Meng Z, Capalbo L, Glover DM, Dunphy WG
Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1.
Mol Biol Cell. 2011 Aug 15;22(16):2834-47. doi: 10.1091/mbc.E11-01-0048. Epub 2011 Jun 16.
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- 21680713 [ View in PubMed]
- Abstract
The mediator protein Claspin is critical for the activation of the checkpoint kinase Chk1 during checkpoint responses to stalled replication forks. This function involves the Chk1-activating domain (CKAD) of Claspin, which undergoes phosphorylation on multiple conserved sites. These phosphorylations promote binding of Chk1 to Claspin and ensuing activation of Chk1 by ATR. However, despite the importance of this regulatory process, the kinase responsible for these phosphorylations has remained unknown. By using a multifaceted approach, we have found that casein kinase 1 gamma 1 (CK1gamma1) carries out this function. CK1gamma1 phosphorylates the CKAD of Claspin efficiently in vitro, and depletion of CK1gamma1 from human cells by small interfering RNA (siRNA) results in dramatically diminished phosphorylation of Claspin. Consequently, the siRNA-treated cells display impaired activation of Chk1 and resultant checkpoint defects. These results indicate that CK1gamma1 is a novel component of checkpoint responses that controls the interaction of a key checkpoint effector kinase with its cognate mediator protein.