Fig 6. Regulation of the mitotic cell cycle by cyclin-dependent kinase inhibitor, CDKN1A (p21^CIP1).

(A) Mechanisms regulating CDKN1A steady-state levels including synthesis, degradations, and association with MPF kinase (CCNB1:CDK1). (B) In vitro kinase activities as determined by Harper et al. [49] for CDKN1A inhibition of MPF (CCNB1:CDK1), Cyclin A:CDK2, and Cyclin E:CDK2 kinases following increasing concentrations of CDKN1A. (C) Simulated increase in CDKN1A synthesis (k_s5) and associated changes in CDKN1A, CDKN1A:MPF, preMPF (CCNB:CDK1P), LMNAP, LMNAT and active MPF kinase resulting in a mitotic collapse. Also, simulated increase in CDKN1A degradation (k_d6.2) and restored oscillations. (D) Restoring oscillations of factors in described in (C) by disrupting the association (k_r5) between CDKN1A:MPF. (E) The range of CDKN1A synthesis (k_s5) with normal mitotic oscillations in factors described in (C).