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Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. [ 5 ] [ 6 ] Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. [ 7 ]
Cyclin-dependent kinase inhibitor 1B (CDKN1B), also known as p27, binds to and prevents the activation of CyclinE:Cdk2 by inhibition. However, as Cyclin A accumulates and binds to Cdk2, they form a complex and inhibit p27. The G1 phase cyclin-dependent kinase works together with S phase cyclin-dependent kinase targeting p27 for degradation.
A protein kinase inhibitor (PKI) is a type of enzyme inhibitor that blocks the action of one or more protein kinases. Protein kinases are enzymes that phosphorylate (add a phosphate , or PO 4 , group) to a protein and can modulate its function.
Checkpoint inhibitor therapy is a form of cancer immunotherapy. The therapy targets immune checkpoints , key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus.
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. CHK2 is involved in DNA repair , cell cycle arrest or apoptosis in response to DNA damage.
Cancer Therapy by Inhibition of Negative Immune Regulation (CTLA4, PD1) A2AR & A2BR: The Adenosine A2A receptor is regarded as an important checkpoint in cancer therapy because adenosine in the immune microenvironment, leading to the activation of the A2a receptor, is negative immune feedback loop and the tumor microenvironment has relatively high concentrations of adenosine. [27]
p21 Cip1 (alternatively p21 Waf1), also known as cyclin-dependent kinase inhibitor 1 or CDK-interacting protein 1, is a cyclin-dependent kinase inhibitor (CKI) that is capable of inhibiting all cyclin/CDK complexes, [5] though is primarily associated with inhibition of CDK2.
At least three checkpoints exist for which the inhibition of Cdk1 by Wee1 is important: G2/M checkpoint : Wee1 phosphorylates the amino acids Tyr15 and Thr14 of Cdk1, which keeps the kinase activity of Cdk1 low and prevents entry into mitosis ; in S. pombe further cell growth can occur.