A question of balance: The role of cyclin-kinase inhibitors in development and tumorigenesis

Cyclin-kinase inhibitors (CKIs) are versatile negative regulators of cell proliferation that function in developmental decisions, checkpoint control and tumour suppression. Phenotypic examination of mice lacking individual CKIs has begun to reveal the specialized roles that each of these proteins play in vivo. This review focuses on what has been learned about the role of CKIs in development and cancer through the generation of knockout animals. The authors discuss whether differences in knockout phenotypes between CKIs reflect differential use of these inhibitors by the organism or a fundamental difference between the inhibitors, and suggest a balance hypothesis to explain the different effects observed.