Fig. 1
From: Models in biology: lessons from modeling regulation of the eukaryotic cell cycle
Molecular aspects of mitotic control in eukaryotic cells. a Biochemists’ view of the regulation of M-phase promoting factor (MPF) in early frog embryos. Derived from the discussion in [2]. Cyclin is synthesized from amino acids (aa) and degraded by a ubiquitin-dependent pathway, catalyzed by the anaphase promoting complex (APC). Cyclin promotes the activation of MPF, which enhances its own production in an autocatalytic fashion. MPF promotes the interphase-to-metaphase transition and activates the APC. b Geneticists’ view of Cdc2 activation in fission yeast cells. Derived from the discussion in [3]. Active Cdc2 promotes the interphase-to-metaphase transition. The activation of Cdc2 is inhibited by Wee1 and promoted by Cdc25. c Solomon’s signal-response curve. Adapted from figure 4B of [12]. A fixed amount of non-degradable cyclin B was added to an interphase-arrested frog egg extract (all protein synthesis is inhibited by cycloheximide). The resultant activity of MPF (the Cdc2:cyclin B heterodimer) was measured as the rate of phosphorylation of histone H1. Notice that there is a distinct cyclin threshold (between 12 and 15 nM) for activation of MPF. d Félix’s experiment. Adapted from figure 1A of [13]; used by permission. An interphase-arrested frog egg extract is doped with a small amount of [35S]cyclin B and then supplemented with increasing amounts of exogenously synthesized MPF. The resultant activity of APC is evident from the rate of degradation of the [35S]cyclin added to the extract. For MPF concentrations between 0 and 6 U/μl (open circles), the rate of cyclin degradation is minimal, and the ‘cyclin remaining’ at each time point is set to 100 %. For larger MPF concentrations, ‘cyclin remaining’ is relative to these control points. For [MPF] = 12 U/μl (closed circles), the [35S]cyclin is rapidly degraded after a time lag of ~25 minutes. For larger concentrations of MPF, 24 U/μl (open squares) and 48 U/μl (closed squares), cyclin is degraded at the same high rate, but the time lag decreases to ~10 minutes