Chk1, one of the downstream protein kinases of ATM/ATR, plays an important role in DNA damage checkpoint, embryonic development and tumor suppression. The activation of Chk1 in response to replication blocks and certain forms of genotoxic stress involves phosphorylation of serines 317 and 345. Activated Chk1 can inactivate cdc25c via phosphorylation at serine 216, blocking the activation of cdc2 and transition into M-phase. Chk1 can also phosphorylate p53 at serine 20 in vitro.
Cell cycle events are regulated by the sequential activation and deactivation of cyclin dependent kinases (Cdks) and by proteolysis of cyclins. Chk1 and Chk2 are involved in these processes as regulators of Cdks. Chk1 and Chk2 both function as essential components in the G2-DNA damage checkpoint by phosphorylating CDC25C in response to DNA damage. CDC25A, CDC25B and CDC25C protein tyrosine phosphatases function as mitotic activators by dephosphorylating CDC2 p34 on regulatory tyrosine residues. Phosphorylation of CDC25C by Chk1 and 2 inhibits its phosphatase activity, thereby blocking mitosis. It has also been shown that Chk1 can phosphorylate Wee1 in vitro, providing evidence that the hyperphosphorylated form of Wee1, seen in cells delayed by Chk1 overexpression, is due to phosphorylation by Chk1.
Storage and Stabilty:Lyophilized powder may be stored at 4°C for short-term only. Stable for 12 months at -20°C. Reconstitute to nominal volume (see reconstitution instructions for peptides) and store at -20°C. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.
