Chk2 was discovered in 1998 as the mammalian homolog of Saccharomyces cerevisiae Rad53 that is active in the yeast DNA damage response (DDR). The protein is conserved in mouse, rat, zebrafish, Xenopus laevis, Drosophila melanogaster, and Caenorhabditis elegans. In humans, it is a single 65 kD polypeptide of 543 residues with three distinct functional domains. During normal growth, Chk2 is present in the nucleus in an inactive monomeric form. After DNA damage, Chk2 is phosphorylated by ATM, which induces Chk2 dimerization and autophosphorylation. When activated, Chk2 phosphorylates nuclear proteins involved in many aspects of the DDR. Many of the Chk2 substrates fall into one of four functional groups involved in DNA repair, cell cycle regulation, p53 signaling, and apoptosis. Chk2 degradation is independent of its activation, its kinase activity, and its phosphorylation state. Chk2 stability is regulated by the E3 ubiquitin ligase SIAH2, which regulates Chk2 basal turnover, with important consequences on cell-cycle control and on the ability of hypoxia to alter the DNA damage-response pathway in cancer cells. In cancers, Chk2 primarily plays roles as tumor suppressor. It negatively regulates androgen sensitivity and prostate cancer cell growth dependent on the downstream signaling proteins CDC25C and Chk1. Chk2 –BRCA1 axis restrains oncogenic Aurora-A activity during mitosis. Chk2-mediated phosphorylation of BRCA1 is required to recruit the PP6C–SAPS3 phosphatase, which acts as a T-loop phosphatase inhibiting Aurora-A bound to BRCA1.

PRODUCT DETAILS

Clone: P81C12B8

Antibody Type: Monoclonal

Reactivity: Human

Format: Alexa Fluor 594

Host: Mouse

Isotype: IgG2b, κ

Applications: ICC - Quality tested

Regulatory Status: RUO

Data Sheets: TDS | SDS

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