It has been a longstanding question in the field as to why OGT is required for dividing mammalian cells. In the past few years, my lab has been trying to address this issue by biochemical and cellular assays, and our data suggest that the underlying molecular mechanisms could be two-fold. First, CDH1 (Cdc20 homologue 1), a co-activator of the Anaphase Promoting Complex/Cyclosome (APC/C) is O-GlcNAcylated, which antagonizes the phosphorylation of CDH1 and enhances the interaction between CDH1 and APC/C. By promoting APC/C<sup>Cdh1 </sup>activity, O-GlcNAc is thus essential for the mitotic exit process. Secondly, after chromosome segregation of the M phase, the cytokinesis stage ensues. Our work shows that OGT is phosphorylated at S20 by a Ser/Thr kinase Chk1 (Checkpoint kinase 1) specifically during cytokinesis. This phosphorylation entails the midbody localization of OGT, stabilizes OGT, and promotes the intermediate filament protein vimentin phosphorylation at S71, which is vital for vimentin severing during the cytokinetic stage. Cells that are depleted of OGT would hence endure vimentin bridge defects and cytokinetic failures. Our on-going work aims to elucidate how OGT fine-tunes the mitotic process, encompassing centrosomes and mitotic master kinases, as well as how mitosis dictates the rise and fall of OGT abundance during cell cycle progression.<br/>

O-GlcNAc: A sweetheart of the cell cycle

2019 Spring National Meeting

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