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

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E07-11-1146v1 19/10/4130    most recent Alert me when this article is cited Alert me if a correction is posted Services Related articles in Mol. Biol. Cell Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Slawson, C. Articles by Hart, G. W. Search for Related Content PubMed PubMed Citation Articles by Slawson, C. Articles by Hart, G. W.

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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