To contribute to a deeper understanding of M-phase control in eukaryotic cells, we have constructed a model based on the biochemistry of M-phase promoting factor (MPF) in Xenopus oocyte extracts, where there is evidence for two positive feedback loops (MPF stimulates its own production by activating Cdc25 and inhibiting Wee1) and a negative feedback loop (MPF stimulates its own destruction by indirectly activating the ubiquitin pathway that degrades its cyclin subunit). To uncover the full dynamical possibilities of the control system, we translate the regulatory network into a set of differential equations and study these equations by graphical techniques and computer simulation. The positive feedback loops in the model account for thresholds and time lags in cyclin-induced and MPF-induced activation of MPF, and the model can be fitted quantitatively to these experimental observations. The negative feedback loop is consistent with observed time lags in MPF-induced cyclin degradation. Furthermore, our model indicates that there are two possible mechanisms for autonomous oscillations. One is driven by the positive feedback loops, resulting in phosphorylation and abrupt dephosphorylation of the Cdc2 subunit at an inhibitory tyrosine residue. These oscillations are typical of oocyte extracts. The other type is driven by the negative feedback loop, involving rapid cyclin turnover and negligible phosphorylation of the tyrosine residue of Cdc2. The early mitotic cycles of intact embryos exhibit such characteristics. In addition, by assuming that unreplicated DNA interferes with M-phase initiation by activating the phosphatases that oppose MPF in the positive feedback loops, we can simulate the effect of addition of sperm nuclei to oocyte extracts, and the lengthening of cycle times at the mid-blastula transition of intact embryos.
Cell Scientists to Watch
Talented researchers who have recently set up their own labs talk about their lives in and out of the lab, the journeys that led them to where they are now, the current state of science funding, and give advice on how to navigate the transition to independence.
'FocalPlane features...' webinar series
We’re excited to announce the new 'FocalPlane features…' webinar series. Covering all aspects of microscopy, join us on the first Tuesday of every month to hear about the latest research and take part in a virtual networking session with the speaker afterwards.
The Corona Files
“In the past year we have called out inequality and injustice, we have forged a public awareness of the value of science, and we have found new ways to interact around the world."
Our resident insectivore, Mole, continues his latest series – The Corona Files. Catch up on Mole’s weekly musings on how COVID-19 is changing the landscape for researchers.
Read & Publish voices: Chris MacDonald
JCS joins the Preprint Reviewer Recruitment Network
Journal of Cell Science, along with its sister journals Development and Biology Open, joins ASAPbio's Preprint Reviewer Recruitment Network, a new initiative aiming to help researchers, journals and publishers, by enabling willing researchers to share preprint feedback as work samples for review by participating journals.
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