Cyclin activation of p34cdc2

Solomon, Mark J.; Glotzer, Michael; Lee, Tina H.; Maury, Philippe; Kirschner, Marc W.

doi:10.1016/0092-8674(90)90504-8

Cited by 678 publications

(598 citation statements)

References 46 publications

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“…For cyclin levels well above threshold, the model shows a lag of about 10 min (Fig. 3), in good agreement with experiments [20,29]. Since we did not use the lag time to determine any rate constants in our model, this agreement with experiments is gratifying.…”

Section: Autonomous Mpf Oscillations and The Cyclin Thresholdsupporting

confidence: 84%

“…The influence of active MPF on Wee1 and Cdc25 creates two positive feedback circuits in the reaction mechanism, making the mitotic control system particularly sensitive to cellular conditions and decisive in its responses. As demonstrated in Novak and Tyson [11], amplification of MPF activity generated by these positive feedback loops accounts for the thresholds and lags reported by Solomon et al [20]. In addition, periodic phosphorylation and dephosphorylation of Tyr-15, driven by these positive feedback loops, 1 Because Thr-14 and Tyr-15 are phosphorylated and dephosphorylated simultaneously, we treat them as a single site, called 'Tyr-15'.…”

Section: Modelmentioning

confidence: 93%

“…The 'cyclin threshold', which is critical to understanding MPF oscillations in Xenopus egg extracts, is best demonstrated experimentally [20] and theoretically [11] in cycloheximide-arrested interphase extracts (no cyclin synthesis) supplemented with exogenously prepared, non-degradable cyclin. Simulating such experiments with our basal parameter values, we find a sharp cyclin threshold for MPF activation: 16 nM non-degradable cyclin cannot activate MPF, but 17 nM does, although only after a long lag period (Fig.…”

Section: Autonomous Mpf Oscillations and The Cyclin Thresholdmentioning

confidence: 99%

See 2 more Smart Citations

Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA

Marlovits

Tyson

Novák

et al. 1998

Biophysical Chemistry

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Alternating phases of DNA synthesis and mitosis, during the first 12 cell divisions of frog embryos, are driven by autonomous cytoplasmic oscillations of M-phase promoting factor (MPF). Cell-free extracts of frog eggs provide a convenient preparation for studying the molecular machinery that generates MPF oscillations and the surveillance mechanism that normally prevents entry into mitosis until chromosomal DNA is fully replicated. Early experiments suggested that unreplicated DNA blocks MPF activity by inducing phosphorylation of a crucial tyrosine residue, but recent evidence implicates a stoichiometric inhibitor (an MPF binding protein) as the 'braking' agent. Using a realistic mathematical model of the mitotic control system in frog egg extracts, we suggest that both tyrosine phosphorylation and a stoichiometric inhibitors are involved in the block of MPF by unreplicated DNA. Both pathways operate by raising the cyclin threshold for MPF activation. As a bonus, in the process of analyzing these experiments, we obtain more direct and reliable estimates of the rate constants in the model.

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Section: Autonomous Mpf Oscillations and The Cyclin Thresholdsupporting

confidence: 84%

Section: Modelmentioning

confidence: 93%

Section: Autonomous Mpf Oscillations and The Cyclin Thresholdmentioning

confidence: 99%

See 1 more Smart Citation

Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA

Marlovits

Tyson

Novák

et al. 1998

Biophysical Chemistry

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“…Two positive-feedback loops contribute to a directional switch (Fig. 3) 31 . Cdc25 is activated by mitotic phosphorylation, whereas Wee1 and Myt1 are inactivated by mitotic phosphorylation.…”

Section: Triggering All-or-nothing Activation Of the Mitotic Kinasementioning

confidence: 99%

“…This idea was supported by tests in an extract system in which translation limited progress of the cycle and by experiments showing that oocyte maturation could be promoted by the introduction of ectopic cyclins 34,46 . When the importance of the positive-feedback loops governing the removal of inhibitory phosphorylation were first recognized, it was suggested that the switch-like behavior acted to interpret the rising levels of cyclin, which would burst the dam at a threshold concentration to induce abrupt activation of cyclin:Cdk1 and entry into mitosis 31 . However, the results of in vivo analysis suggest that cyclin levels are generally not key inputs into the decision to enter mitosis.…”

Section: Throwing Light Upon Flipping the Switchmentioning

confidence: 99%

Triggering the all-or-nothing switch into mitosis

O’Farrell

2001

Trends in Cell Biology

168

147

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The past decade of cell cycle investigations has identified many roads not taken. The kinase that drives mitosis can be modulated by cyclins, by activating phosphorylation, by inhibitory phosphorylation and by binding of inhibitors, but one of these regulatory options controls the transition from G2 phase to mitosis in most circumstances. A switch-like mechanism integrates signals of cellular status and commits the cell to mitosis by abruptly removing inhibitory phosphate from preformed cyclin:Cdk1 complexes. The pathways that flip this switch alter the balance of modifying reactions to favor dephosphorylation, thereby generating a flood of mitotic kinase.

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Advancement through Mitosis requiresrae1 Gene Function in Fission Yeast

Whalen

Bharathi

Danielewicz

et al. 1997

Yeast

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Growth of the rae1‐1 mutant of Schizosaccharomyces pombe at restrictive temperature results in accumulation of poly(A)+ RNA in the nucleus and a cell cycle arrest at the G2/M boundary. We demonstrate here that rae1 function is required for a process other than mRNA export which is essential for advancement through mitosis. Cells lacking rae1 function arrest with elevated Cdc2p kinase levels at a step before the formation of a mitotic spindle and without separation of the spindle pole bodies. Rae1p was localized to the nuclear periphery, consistent with a role in nucleocytoplasmic trafficking, which could include protein import. We propose a model where rae1 functions in cell cycle progression through trafficking of proteins required for mitosis. © 1997 John Wiley & Sons, Ltd.

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Cyclin activation of p34cdc2

Cited by 678 publications

References 46 publications

Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA

Modeling M-phase control in Xenopus oocyte extracts: the surveillance mechanism for unreplicated DNA

Triggering the all-or-nothing switch into mitosis

Advancement through Mitosis requiresrae1 Gene Function in Fission Yeast

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