What is the function of Chk1?
Checkpoint kinase 1 (Chk1) is a serine/threonine protein kinase that is also regulated by reversible phosphorylation. Chk1 was first identified in fission yeast as an essential component of the DNA damage checkpoint (3, 45).
Is phosphorylation of Chk1 required for kinase activation?
Phosphorylation of Chk1 at ATM/ATR Consensus Phosphorylation Sites is Required for Kinase Activation in Response to Stress
Can Chk1/Chk2 and Wee1 be targeted together?
Synergism in targeting CHK1/CHK2 and WEE1 together in NPC cells A general approach for target therapies is to utilize minimum drug concentrations to reduce non-specific effects and general toxicity. A growing body of evidence indicates that targeting CHK1/CHK2 and WEE1 together can increase cytotoxicity in a variety of cancer cell types [16].
Can s345 phosphorylation stimulate Chk1 catalytic activity?
Chk1 S345 phosphorylation de-represses latent kinase activity under native conditions S345 phosphorylation could stimulate Chk1 catalytic activity by inducing a conformational change in the kinase domain to an inherently more active configuration, or alternatively, by modulating interaction with regulatory factors.
How many Ser/Gln residues are in Chk1?
Chk1 contains four Ser/Gln residues. Chk 1 activation occurs primarily through the phosphorylation of the conserved sites, Ser-317, Ser-345 and less often at Ser-366. Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. Two checkpoint kinase subtypes have been identified, Chk1 and Chk2.
What is Chk1 and RAD27?
In 1993, Beach and associates initially identified Chk1 as a serine/threonine kinase which regulates the G2/M phase transition in fission yeast. Constitutive expression of Chk1 in fission yeast was shown to induce cell cycle arrest. The same gene called Rad27 was identified in budding yeast by Carr and associates.
What is the role of regulatory phosphorylation of Chk1 in checkpoint activation?
Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity. Oncogene. 2009;28:2314–23.