Figure 1.

Cell-cycle regulation by the CWI pathway in response to perturbations in the cell surface. This scheme represents the mechanism by which the CWI pathway impinges on cell-cycle regulators to respond to stresses in the cell surface. The CWI pathway has a negative role in the Start transcriptional program, through inducing the expression of the transcriptional repressor Whi7 and promoting the nuclear export of the transcription factor Swi6. It also negatively regulates the initiation of DNA replication, by stabilizing the CKI Sic1 and inhibiting the DNA replication factor Cdc6. The CWI pathway plays a negative role in the G2 transcriptional program, inhibiting the Hcm1 and Ndd1 transcription factors, which results in the impaired expression of mitotic cyclins, among many other mitotic genes. Finally, it affects other aspects of mitotic entry and progression, acting by regulating Swe1, and probably Mih1, to control the inhibition of CDK Cdc28 through Tyr-19 phosphorylation, and by the activation of phosphatase PP2A^Cdc55, which positively and negatively affects Swe1 and Mih1 and inhibits mitotic progression. Although some molecular details and the specific relevance to cell-cycle regulation of some of these mechanisms are yet to be fully characterized, a scenario has emerged in which the CWI pathway is an important player mediating the arrest of the cell cycle in response to cell-wall/plasma membrane stresses.