This gene encodes a potent cyclin-dependent kinase inhibitor. The encoded protein binds to and inhibits the activity of cyclin-CDK2 or -CDK4 complexes, and thus functions as a regulator of cell cycle progression at G1. The expression of this gene is tightly controlled by the tumor suppressor protein p53, through which this protein mediates the p53-dependent cell cycle G1 phase arrest in response to a variety of stress stimuli. This protein can interact with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in S phase DNA replication and DNA damage repair. This protein was reported to be specifically cleaved by CASP3-like caspases, which thus leads to a dramatic activation of CDK2, and may be instrumental in the execution of apoptosis following caspase activation. Multiple alternatively spliced variants have been found for this gene. [provided by RefSeq, Nov 2010].
Porter, Farmaki, Altilia, Schools, West, Chen, Chang, Puzyrev, Lim, Rokow-Kittell, Friedhoff, Papavassiliou, Kalurupalle, Hurteau, Shi, Baran, Gyorffy, Wentland, Broude, Kiaris, Roninson: "Cyclin-dependent kinase 8 mediates chemotherapy-induced tumor-promoting paracrine activities." in: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, Issue 34, pp. 13799-804, (2012) (PubMed).