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Sci. Signal., 12 January 2010
Vol. 3, Issue 104, p. ra2
[DOI: 10.1126/scisignal.2000526]


Extensive Crosstalk Between O-GlcNAcylation and Phosphorylation Regulates Cytokinesis

Zihao Wang1*, Namrata D. Udeshi2*, Chad Slawson1*, Philip D. Compton2, Kaoru Sakabe1, Win D. Cheung1, Jeffrey Shabanowitz2, Donald F. Hunt2, and Gerald W. Hart1{dagger}

1 Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2 Department of Chemistry, University of Virginia, Charlottesville, VA 22904, USA.

* These authors contributed equally to this work.

Abstract: Like phosphorylation, the addition of O-linked β-N-acetylglucosamine (O-GlcNAcylation) is a ubiquitous, reversible process that modifies serine and threonine residues on nuclear and cytoplasmic proteins. Overexpression of the enzyme that adds O-GlcNAc to target proteins, O-GlcNAc transferase (OGT), perturbs cytokinesis and promotes polyploidy, but the molecular targets of OGT that are important for its cell cycle functions are unknown. Here, we identify 141 previously unknown O-GlcNAc sites on proteins that function in spindle assembly and cytokinesis. Many of these O-GlcNAcylation sites are either identical to known phosphorylation sites or in close proximity to them. Furthermore, we found that O-GlcNAcylation altered the phosphorylation of key proteins associated with the mitotic spindle and midbody. Forced overexpression of OGT increased the inhibitory phosphorylation of cyclin-dependent kinase 1 (CDK1) and reduced the phosphorylation of CDK1 target proteins. The increased phosphorylation of CDK1 is explained by increased activation of its upstream kinase, MYT1, and by a concomitant reduction in the transcript for the CDK1 phosphatase, CDC25C. OGT overexpression also caused a reduction in both messenger RNA expression and protein abundance of Polo-like kinase 1, which is upstream of both MYT1 and CDC25C. The data not only illustrate the crosstalk between O-GlcNAcylation and phosphorylation of proteins that are regulators of crucial signaling pathways but also uncover a mechanism for the role of O-GlcNAcylation in regulation of cell division.

{dagger} To whom correspondence should be addressed. E-mail: gwhart{at}

Citation: Z. Wang, N. D. Udeshi, C. Slawson, P. D. Compton, K. Sakabe, W. D. Cheung, J. Shabanowitz, D. F. Hunt, G. W. Hart, Extensive Crosstalk Between O-GlcNAcylation and Phosphorylation Regulates Cytokinesis. Sci. Signal. 3, ra2 (2010).

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