کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5371138 | 1503935 | 2013 | 6 صفحه PDF | دانلود رایگان |
- Modelling the interplay of Cdk1:CycB, Cdc20, APC/C, Emi2 and PP2A-Bâ²56 in the control of early embryonic cell cycle
- The period and amplitude of early embryonic cell cycle are sensitive to Emi2 levels.
- Emi2 interferes with intrinsic time delay in APC/C activation and inactivation.
The early embryonic Xenopus cell cycles are characterized by alternating oscillations of Cyclin-dependent kinase-1 (Cdk1) and Anaphase Promoting Complex/Cyclosome (APC/C) activities. The early cycles before midblastula transition lack significant inhibitory Cdk1 phosphorylations and are driven by periodic accumulation of Cyclin B before M phase and its degradation by APC/C at the end of M phase. Both experiments and mathematical modelling suggest that while Cdk1:CycB phosphorylation activates APC/C, it inhibits its co-activator Cdc20 (Fizzy). These interactions create an amplified negative-feedback loop which is at the heart of all cell cycle oscillations. Recent experiments find that the APC/C inhibitor, Emi2/XErp1 is essential for large amplitude and short period Cyclin B oscillations during early divisions in the intact Xenopus embryo. This finding is counter-intuitive since larger amplitudes should come with slower cycle times. We explain this paradox by analysing the amplified negative feedback model extended with APC/C inhibition by Emi2. We show that Emi2 interferes with the intrinsic time-delay in APC/C activation and inactivation to increase the amplitude as well as shorten the period of Cyclin B oscillation.
Journal: Biophysical Chemistry - Volumes 177â178, JulyâAugust 2013, Pages 1-6