Punctuated cyclin synthesis drives early embryonic cell cycle oscillations
| Autor: | Joseph R. Pomerening, Qing Kang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Embryo
Nonmammalian Cyclin E Cyclin D Cyclin A Cyclin B Mitosis Biology Xenopus laevis 03 medical and health sciences CDC2 Protein Kinase Animals RNA Messenger Cyclin B1 Molecular Biology 030304 developmental biology Feedback Physiological 0303 health sciences Cell Cycle 030302 biochemistry & molecular biology G1/S transition Articles Cell Biology Molecular biology Adenosine Monophosphate Cell biology Polyribosomes Protein Biosynthesis Cyclin-dependent kinase complex biology.protein biological phenomena cell phenomena and immunity Cell Division Cyclin A2 |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| DOI: | 10.1091/mbc.e11-09-0768 |
| Popis: | Cyclin B accumulation in the early Xenopus embryo drives CDK1 oscillations. CDK1 directs a negative-feedback loop upon cyclin B synthesis through the repression of global protein translation, and this attenuation of cyclin B synthesis could improve the efficiency and robustness of this cell cycle oscillator. Cyclin B activates cyclin-dependent kinase 1 (CDK1) at mitosis, but conflicting views have emerged on the dynamics of its synthesis during embryonic cycles, ranging from continuous translation to rapid synthesis during mitosis. Here we show that a CDK1-mediated negative-feedback loop attenuates cyclin production before mitosis. Cyclin B plateaus before peak CDK1 activation, and proteasome inhibition caused minimal accumulation during mitosis. Inhibiting CDK1 permitted continual cyclin B synthesis, whereas adding nondegradable cyclin stalled it. Cycloheximide treatment before mitosis affected neither cyclin levels nor mitotic entry, corroborating this repression. Attenuated cyclin production collaborates with its destruction, since excess cyclin B1 mRNA accelerated cyclin synthesis and caused incomplete proteolysis and mitotic arrest. This repression involved neither adenylation nor the 3′ untranslated region, but it corresponded with a shift in cyclin B1 mRNA from polysome to nonpolysome fractions. A pulse-driven CDK1–anaphase-promoting complex (APC) model corroborated these results, revealing reduced cyclin levels during an oscillation and permitting more effective removal. This design also increased the robustness of the oscillator, with lessened sensitivity to changes in cyclin synthesis rate. Taken together, the results of this study underscore that attenuating cyclin synthesis late in interphase improves both the efficiency and robustness of the CDK1-APC oscillator. |
| Databáze: | OpenAIRE |
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