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Vol. 19, Issue 10, 4130-4140, October 2008

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A Mitotic GlcNAcylation/Phosphorylation Signaling Complex Alters the Posttranslational State of the Cytoskeletal Protein Vimentin

Chad Slawson^*, T. Lakshmanan, Spencer Knapp, and Gerald W. Hart^*

*Department of Biological Chemistry, The Johns Hopkins School of Medicine, Baltimore, MD 21205; Momenta Pharmaceuticals, Cambridge, MA 02142; and Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, NJ 08554

Submitted November 15, 2007; Revised July 9, 2008; Accepted July 10, 2008
Monitoring Editor: M. Bishr Omary

InCytes from MBC

O-linked β-N-acetylglucosamine (O-GlcNAc) is a highly dynamic intracellular protein modification responsive to stress, hormones, nutrients, and cell cycle stage. Alterations in O-GlcNAc addition or removal (cycling) impair cell cycle progression and cytokinesis, but the mechanisms are not well understood. Here, we demonstrate that the enzymes responsible for O-GlcNAc cycling, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) are in a transient complex at M phase with the mitotic kinase Aurora B and protein phosphatase 1. OGT colocalized to the midbody during telophase with Aurora B. Furthermore, these proteins coprecipitated with each other in a late mitotic extract. The complex was stable under Aurora inhibition; however, the total cellular levels of O-GlcNAc were increased and the localization of OGT was decreased at the midbody after Aurora inhibition. Vimentin, an intermediate filament protein, is an M phase substrate for both Aurora B and OGT. Overexpression of OGT or OGA led to defects in mitotic phosphorylation on multiple sites, whereas OGT overexpression increased mitotic GlcNAcylation of vimentin. OGA inhibition caused a decrease in vimentin late mitotic phosphorylation but increased GlcNAcylation. Together, these data demonstrate that the O-GlcNAc cycling enzymes associate with kinases and phosphatases at M phase to regulate the posttranslational status of vimentin.

Address correspondence to: Gerald W. Hart (gwhart{at}jhmi.edu)

Abbreviations used: GFP, green fluorescent protein; GT, O-GlcNAc-thiazoline; OGA, O-GlcNAcase; O-GlcNAc, O-linked β-N-acetylglucosamine; OGT, O-GlcNAc transferase; PP1, protein phosphatase 1; ZM, ZM447439.

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InCytes from MBC, October 2008

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