Mitotic regulation of the protein-phosphatase scaffold RepoMan - Professor Mathieu Bollen

Tuesday 2nd June 2015

Mitotic regulation of the protein-phosphatase scaffold RepoMan

Professor Mathieu Bollen

University of Leuven, Belgium

When: Tuesday, 2 June, 2015 - 16:00

Where: Level 6 Seminar Room, Jacqui Wood Cancer Centre

Abstract

RepoMan is a mitotic interactor of protein phosphatases PP1 and PP2A-B56. During prometaphase PP2A-B56 promotes the chromosome targeting of RepoMan, whereas RepoMan-associated PP1 opposes the centromeric targeting of Aurora B through dephosphorylation of Histone H3 at Thr3. Here, we show that the Cdk1-mediated phosphorylation of RepoMan reduces the binding of PP1 but enhances the recruitment of PP2A-B56. Upon inactivation of Cdk1 at the beginning of anaphase PP2A-B56 dissociates from RepoMan and the binding of PP1 is increased, culminating in the bulk recruitment of RepoMan to the chromosomes. This phosphatase switch serves to make the chromosome-binding of RepoMan Cdk1-independent and irreversible. We also show that the reduced PP1-RepoMan interaction during prometaphase prevents the precocious dephosphorylation of Aurora B and Importin b, which are substrates of RepoMan-associated PP1 in anaphase. Hence, the Cdk1-mediated phosphorylation of RepoMan contributes to the ordered dephosphorylation of mitotic-exit substrates.