Fig 7. Activation of APC/C and substrate degradations.

(A) Approximated steady-state protein levels from studies by Zhao et al. [40] using immunoblot analysis of PLK1T, CCNB1T, CDC20T CDH1T and PTTG1T in HeLa cells following release from synchronization in G1/S. Arrows mark points of comparison between in vitro and in silico data. (P, phosphorylated protein; T, total protein) (B) Immunoblot analysis as described in (A) by Zhao et al. [33] and including APC3T (i.e. APC/CT) and APC3P (i.e. APC/CP) but following release from M phase. (C) Simulation of APC/C ubiquitin ligase regulation including changes in PPase, APC/CP, APC/CT, PTTG1T, CDC20T, CDH1T, CCNBT, PLK1T and MPF kinase (CCNB1:CDK1). Boxed area is magnified. (P, phosphorylated protein; T, total protein). (D) Kinetics of CCNB1T levels from studies by Hein et al. [13] using HeLa cells expressing wild-type CDC20 or mutated CDC20 3SP (T55S, T59S, T70S) following release from synchronization in G1/S. (E) Simulated changes over time upon reducing PPase activity ($k_{f9}^{\prime }$) (i.e. PP2A) and associated changes in PPase, CDC20T, CCNB1T and MPF kinase (CCNB1:CDK1).