Figure 6.

Proposed model for conformational regulation of checkpoint kinase 1 (Chk1) by N-terminal Chk1-binding peptide (Chk1-NP). Autoinhibitory closed conformation of Chk1 is maintained by the intramolecular interaction between the N-terminal kinase domain and the C-terminal domain (CD). Binding of Chk1-NP to the very N-terminal part of the Chk1 kinase domain disrupts the closed conformation and releases the C-terminal domain. Serine (S)345 residue is phosphorylated and the pChk1 is exported to the cytoplasm. Open conformation of Chk1 upon Chk1-NP binding may facilitate the phosphorylation of Chk1 at S345, which leads to the activation of Chk1. pChk1 may follow the following fates: transduction of Chk1 signaling to downstream targets, export to the cytoplasm and its degradation. Therefore Chk1-NP may enhance radiation sensitivity by changing conformation, localization, activity and the protein stability of Chk1.