anti-Chk2 (Checkpoint Kinase 2), mAb (20A8)

Both Chk1 and Chk2 are critically important checkpoint kinases. Chk1 is essential for normal development and cell growth and Chk1 deficiency in mouse or in embryonic stem (ES) cells is lethal. Loss of Chk2 is tolerated and has been found to be associated with a subset of Li-Fraumeni cases. Li-Fraumeni syndrome increases greatly the susceptibility to cancer, with particularly high occurrences of breast cancer, brain tumors, acute leukemia, soft tissue sarcomas, bone sarcomas, and adrenal cortical carcinoma. Chk2 regulates cell cycle checkpoints and apoptosis in response to DNA damage, particularly to DNA double-strand breaks. The cell either stops the cell cycle and therefore its proliferation until the damage is repaired, or it destructs itself (apoptosis). The ataxia telangiectasia mutated (ATM) and ATR (ATM and Rad3-related) protein kinases exert cell cycle delay, in part, by phosphorylating Chk1, Chk2, and p53. Phosphorylation on Chk1 and p53 requires ATR, whereas phosphorylation on Chk2 requires ATM. Screening of novel substrates of Chk1 and Ckh2 followed by imunoprecipitation kinase assay and site-directed mutagenesis analysis suggests that HDAC5 and PGC-1 are specific targets for Chk1 and/or Chk2 at least in vitro. Regulates cell cycle checkpoints and apoptosis in response to DNA damage, particularly to DNA double-strand breaks. Inhibits CDC25C phosphatase by phosphorylation on 'Ser-216', preventing the entry into mitosis. May also play a role in meiosis. Regulates the TP53 tumor suppressor through phosphorylation at 'Thr-18' and 'Ser-20'.