CHK2, CHK2 checkpoint homolog

名称: CHK2；细胞周期检测点激酶2 种属：human

描述: DNA damage or incomplete replication of DNA results in the inhibition of cell cycle progression at the G1 to S or the G2 to M phase transition by conserved regulatory mechanisms known as cell cycle checkpoints. Checkpoint proteins include Rad17, which is involved in regulating cell cycle progression at the G1 checkpoint, and Chk1, Chk2, Rad1, Rad9 and Hus1, which are involved in regulating cell cycle arrest at the G2 checkpoint. CHEK2 is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases.

细胞周期检测点激酶1和2(CHK1和CHK2)是细胞周期检测点中非常重要的蛋白激酶,它们通过信号传导和放大,调节下游靶蛋白表达,使细胞周期出现阻滞。抑制CHK1和CHK2蛋白表达,可有效地消除肿瘤细胞在放射线或化疗药物作用后的细胞周期阻滞,增加放化疗的敏感性

参考文献: #: Sakasai R et al. Transcription-dependent activation of ataxia telangiectasia mutated prevents DNA-dependent protein kinase-mediated cell death in response to topoisomerase I poison. J Biol Chem 285:15201-8 (2010). PubMed: 20304914

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