Mitotic Exit Function of Polo-like Kinase Cdc5 Is Dependent on Sequential Activation by Cdk1

• Published in: Cell reports (Cambridge) Vol. 15; no. 9; pp. 2050 - 2062
• Main Authors: Rodriguez-Rodriguez, Jose-Antonio, Moyano, Yolanda, Játiva, Soraya, Queralt, Ethel
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.05.2016; Elsevier
• Subjects: Amino Acid Sequence; Anaphase; Cdc fourteen early anaphase release; Cdc14 phosphatase; CDC2 Protein Kinase - metabolism; CDC28 Protein Kinase, S cerevisiae - metabolism; Cdc5 polo kinase; Cell Cycle Proteins - metabolism; Cell Nucleolus - metabolism; Enzyme Activation; Metaphase; Mitosis; mitotic exit network; Peptides - chemistry; Phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae Proteins - metabolism; Cdc5 polo kinase; Cdc fourteen early anaphase release; Cdc14 phosphatase; mitosis; mitotic exit network
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2016.04.079

To complete mitosis, Saccharomyces cerevisiae needs to activate the mitotic phosphatase Cdc14. Two pathways contribute to Cdc14 regulation: FEAR (Cdc14 early anaphase release) and MEN (mitotic exit network). Cdc5 polo-like kinase was found to be an important mitotic exit component. However, its specific role in mitotic exit regulation and its involvement in Cdc14 release remain unclear. Here, we provide insight into the mechanism by which Cdc5 contributes to the timely release of Cdc14. Our genetic and biochemical data indicate that Cdc5 acts in parallel with MEN during anaphase. This MEN-independent Cdc5 function requires active separase and activation by Cdk1-dependent phosphorylation. Cdk1 first phosphorylates Cdc5 to activate it in early anaphase, and then, in late anaphase, further phosphorylation of Cdc5 by Cdk1 is needed to promote its MEN-related functions. [Display omitted] •Cdc5-mediated Cdc14 activation is regulated by sequential Cdk1 phosphorylation•Phosphorylation of Cdc5 at T242 and T70 regulate its kinase activity•Cdk1 initially phosphorylates Cdc5 at its activation loop, mostly at T242•Cdc5 T70 phosphorylation by Cdk1 is important for Cdc5-MEN function The specific role of Cdc5 in mitotic exit and Cdc5 involvement in Cdc14 release has been unclear. Rodriguez-Rodriguez et al. demonstrate that Cdc5 function is regulated by sequential Cdk1 phosphorylation. Initial phosphorylation at T242 activates Cdc5, which, in turn, promotes Cdc14 release. Later, phosphorylation at T70 contributes to Cdc5-MEN function.