Kinases and Phosphatases Cooperate to Shape Phosphoproteome Dynamics during Mitotic Exit

October 10th, 2019 - 11AM

Sandra Touati, Laboratoire Biologie du Développement, IBPS

Abstract: Temporal control over protein phosphorylation and dephosphorylation is crucial for accurate chromosome segregation and for completion of the cell division cycle during exit from mitosis.

Degradation of mitotic cyclins and activation of Cdk?counteracting phosphatases lead to protein dephosphorylation. In budding yeast, the Cdc14 phosphatase is thought to be a major regulator at this time, while in higher eukaryotes PP2A phosphatases take a dominant role. We use time-resolved phosphoproteome analysis in budding yeast to evaluate the respective contributions of the kinases and phosphatase input. This reveals that successive inactivation of Cdks and of the mitotic kinase Polo contributes to order mitotic exit dephosphorylation events. Cdc14 instructs the sequential pattern of phosphorylation changes, in part through its preferential recognition of serine-based cyclin-dependent kinase (Cdk) substrates. PP2ACdc55 in turn exhibit a broad substrate spectrum with some selectivity for phospho-threonines. Our results illustrate synergy and coordination between kinases and phosphatases to orchestrate the phosphoproteome by recognising some specific docking motifs, phosphoresidus and amino acid regions surrounding the phosphosite.

Location: LCQB Kitchen, building C, 4th floor, Pierre et Marie Curie Campus

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Seminar organised by the Laboratory of Computational and Quantitative Biology