Spatial control of mitotic commitment in fission yeast

Abstract

The activation of the Cdk1 (cyclin-dependent kinase 1)-cyclin B complex to promote commitment to mitosis is controlled by the phosphorylation status of the Cdk1 catalytic subunit. Cdk1 phosphorylation by Wee1 kinases blocks activation until Cdc25 (cell division cycle 25) phosphatases remove this phosphate to drive division. Feedback inhibition of Wee1 and promotion of Cdc25 activities by the newly activated Cdk1-cyclin B complexes ensure that the transition from interphase to mitosis is a rapid and complete bi-stable switch. Although this level of molecular understanding of the mitotic commitment switch has been clear for over two decades, it is still unclear how the switch is engaged to promote division at the right time for a particular context. We discuss recent work in fission yeast that shows how the spatial organization of signalling networks, in particular events on the centrosome equivalent, the spindle pole body, plays a key role in ensuring that the timing of cell division is coupled to environmental cues.

Cyclin B1-Cdk1 binding to MAD1 links nuclear pore disassembly to chromosomal stability

“…Thus, our study identifies an important function for localised Cyclin B1-CDK1 activity and adds to our understanding of the increasing importance of local kinase-phosphatase gradients in controlling the cell (reviewed in Pines and Hagan, 2011). Spatial control of Cyclin B-CDK1 has been clearly demonstrated in triggering mitosis from the spindle pole body in fission yeast (Grallert et al, 2013;Hagan and Grallert, 2013) as has the spatial control of Plk1 through its recruitment to substrates previously phosphorylated by CDK1 (Elia et al, 2003a(Elia et al, , 2003b, and in the control of error correction at kinetochores through the balance of Aurora B and PP1/PP2A phosphatases activities (Liu et al, 2010;Welburn et al, 2010;reviewed in Gelens et al, 2018;Liu et al, 2010).…”

Cyclin B1-Cdk1 facilitates MAD1 release from the nuclear pore to ensure a robust spindle checkpoint

“…Thus, our study likely identifies an important function for localized cyclin B1-Cdk1 activity and adds to our understanding of the increasing importance of local kinase-phosphatase gradients in controlling the cell (reviewed in Pines and Hagan, 2011). Spatial control of cyclin B1-Cdk1 has been clearly demonstrated in triggering mitosis from the spindle pole body in fission yeast (Grallert et al, 2013; Hagan and Grallert, 2013), as has the spatial control of Plk1 through its recruitment to substrates previously phosphorylated by Cdk1 (Elia et al, 2003a,b), and in the control of error correction at kinetochores through the balance of Aurora B and PP1/PP2A phosphatases activities (Liu et al, 2010; Welburn et al, 2010; reviewed in Gelens et al, 2018; Liu et al, 2010).…”

Causes and consequences of centrosome abnormalities in cancer

“…One clear example of signalling promoted by the centrosome is the regulation of mitotic entry in fission yeast [122]. A compelling body of work suggests that the spindle pole body (SPB) functions as a platform to increase a feedback loop that amplifies cyclin B/Cdk1 activity, which is then propagated throughout the cell.…”