Degradation cyclin

Abrieu A, Lorca T, Labbe J-C, Morin N, Keyse S, Doree M 1996 MAP kinase does not inactivate, but rather prevents the cyclin degradation pathway from being turned on in Xenopus egg extract. J Cell Sci 109 239—246... 

The progression of the cell cycle is regulated by interconversion processes, in each phase, special Ser/Thr-specific protein kinases are formed, which are known as cyclin-depen-dent kinases (CDKs). This term is used because they have to bind an activator protein (cyclin) in order to become active. At each control point in the cycle, specific CDKs associate with equally phase-specific cyclins. if there are no problems (e.g., DNA damage), the CDK-cyclin complex is activated by phosphorylation and/or dephosphorylation. The activated complex in turn phosphorylates transcription factors, which finally lead to the formation of the proteins that are required in the cell cycle phase concerned (enzymes, cytoskeleton components, other CDKs, and cyclins). The activity of the CDK-cyclin complex is then terminated again by proteolytic cyclin degradation. 

Spindle formation Chromosome condensation Disappearance of nuclear membrane Transcription stop Cyclin degradation... 

Hershko, A., Ganoth, D., Pehrson, J., Palazzo, R.E. and Cohen, L.H. (1991). Methylated ubiquitin inhibits cyclin degradation in clam oocyte extracts. J. Biol. Chem. 266,16376-16379. 

A conspicuous feature of cyclin and cdc2 interactions is the occurrence of sharp thresholds in the dependence of cdc2 kinase activation by cyclin, and in the dependence of cyclin degradation on active cdc2 kinase (Minshull et al, 1989 Murray Kirschner, 1989b Felix et al, 1990 Karsenti, Verde Felix, 1991 King et al, 1994). Besides the... 

The model thus shows how thresholds in the phosphorylation-dephosphorylation cascade controlling cdc2 kinase play a primary role in the mechanism of mitotic oscillations. The model further shows how these thresholds are necessarily associated with time delays whose role in the onset of periodic behaviour is no less important. The first delay indeed originates from the slow accumulation of cyclin up to the threshold value C beyond which the fraction of active cdc2 kinase abruptly increases up to a value close to unity. The second delay comes from the time required for M to reach the threshold M beyond which the cyclin protease is switched on. Moreover, the transitions in M and X do not occur instantaneously once C and M reach the threshold values predicted by the steady-state curves the time lag in each of the two modification processes contributes to the delay that separates the rise in C from the increase in Af, and the latter increase from the rise in X. The fact that the cyclin protease is not directly inactivated when the level of cyclin drops below C prolongs the phase of cyclin degradation, with the consequence that M and X will both become inactivated to a further degree as C drops well below C. ... 

Parameters of the first kind are the rate of cyclin synthesis (Vj), the maximum rate of cyclin degradation by the specific protease X (vj), the Michaelis constant of the latter enzyme (K ), and the apparent first-order rate constant for nonspecific cyclin degradation (k ). Clearly the nonspecific degradation of cyclin should remain negligible, since (at least in the absence of positive feedback) no oscillations would occur if such a process predominated over the specific action of protease X. This is confirmed by the construction of stability diagrams showing that the domain of oscillations in parameter space shrinks as the value of fcj increases, until a value of that rate constant is reached beyond which oscillations disappear (Romond et al, 1994). 

As discussed in section 10.6, the increase in Ca at fertilization appears to induce some phosphorylation event(s) via calmodulin-activated protein kinase (Lorca et al., 1993). One result of this is the activation of the cyclin degradation pathway, which releases the oocyte from metaphase arrest. A recent study in rabbit oocytes (Collas et at, 1995) was aimed at measuring MPF-associated kinase activity as a function of the number of Ca pulses applied to the oocytes. The results suggest that, whereas a single Ca pulse elicits only a transient decrease in MPF activity, a prolonged series of Ca spikes is needed to sustain the MPF inactivation associated with exit from the metaphase arrested state. 

F61ix, M.A., J.C. Labbe, M. Doree,T. Hunt E. Karsenti. 1990. Triggering of cyclin degradation in interphase extracts of amphibian eggs by cdc2 kinase. Nature 346 379 82. 

Lorca, T., D. Fesquet, F. Zindy, F. Le Bouffant, M. Cerruti, C. Brechot, G. Devauchelle M. Doree. 1991a. An okadaic acid-sensitive phosphatase negatively controls the cyclin degradation pathway in amphibian eggs. Mol. Cell. Biol. 11 1171-5. 

Yu H et al (1996) Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. Curr Biol 6 455-466... 

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