New elements in the mitotic control of the fission yeast Schizosaccharomyces pombe.

The p107wee1 protein kinase plays a central role in regulating the cell cycle of fission yeast. It mediates transmission of signal(s) related to the nutritional status of the cell to the p34cdc2 protein kinase, which is an active component of the MPF complex driving cells into mitosis. p107wee1 is itself subject to control by the products of other genes such as nim1+/cdr1+, win1+, and perhaps wis1+ and other wis+ genes. At present, the relationships between these genes and their possible roles in the mitotic control are unclear and must await further analysis (Fig. 5). It is likely that some of the gene products are concerned with the sensing and/or transmission of nutritional signals. p107wee1 negatively regulates the activity of p34cdc2, probably by direct tyrosine phosphorylation, and also appears to regulate the activities of the cdc1+ and cdc27+ gene products. The effects of nitrogen starvation and of wee1 mutations on conditional lethal mutations at the cdc1, cdc2, and cdc27 loci, taken together, support the largely speculative model shown in Figure 5. During the normal cycle, the balance between phosphorylated and dephosphorylated p34cdc2 changes such that at the appropriate time, p34cdc2 is activated and the cell enters mitosis. We suggest that the cdc1+ and cdc27+ products may be regulated in a similar way. Such a mechanism would ensure coordinated activation of these and perhaps other proteins required for the G2/M transition. There are, of course, many uncertainties, and these must await elucidation by biochemical and genetic analysis.