Chk1: a protein kinase of the CAMKL family. Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. Plays an important role in both S and G2 checkpoints, embryonic development and tumor suppression. Phosphorylated and activated by ATM/ATR following DNA damage, it binds to single-stranded DNA and DNA ends and has a role in the repair of double strand breaks. Activated Chk1 can phosphorylate and inactivate cdc25C via phosphorylation and 14-3-3 binding, blocking the activation of cdc2 and transition into M-phase. Other substrates include p53. Implicated in resistance to apoptosis in response to chemotherapy. Inhibitors under development to chemosensitize tumors. Somatic mutations found in stomach tumors, and in colon and endometrial tumors, where CHK1 may be a target of microsatellite instability. Inhibitors: SB218078, UNC-01.
Protein type: EC 2.7.11.1; Kinase, protein; Tumor suppressor; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); CAMK group; CAMKL family; CHK1 subfamily
Chromosomal Location of Human Ortholog: 11q24.2
Cellular Component: nucleoplasm; extracellular space; centrosome; chromosome, telomeric region; condensed nuclear chromosome; intracellular membrane-bound organelle; replication fork; cytosol; nucleus; chromatin
Molecular Function: protein serine/threonine kinase activity; protein binding; ATP binding
Biological Process: DNA damage induced protein phosphorylation; chromatin-mediated maintenance of transcription; regulation of mitotic centrosome separation; DNA damage checkpoint; negative regulation of mitosis; peptidyl-threonine phosphorylation; G2/M transition of mitotic cell cycle; DNA repair; G2/M transition DNA damage checkpoint; DNA replication; response to DNA damage stimulus; regulation of cell proliferation
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