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Serum-stimulated cell cycle entry promotes ncOGT synthesis required for cyclin D expression. Oncogenesis 2012 Dec 10;1:e36

Date

01/01/2012

Pubmed ID

23552487

Pubmed Central ID

PMC3545199

DOI

10.1038/oncsis.2012.36

Scopus ID

2-s2.0-84871950193   39 Citations

Abstract

Nuclear and cytoplasmic O-GlcNAc transferase (OGT) is a unique and universally expressed enzyme catalyzing O-GlcNAcylation of thousands of proteins. Although OGT interferes with many crucial intracellular processes, including cell cycle, only few studies have focused on elucidating the precise role of the glycosyltransferase during cell cycle entry. We first demonstrated that starved MCF7 cells reincubated with serum quickly induced a significant OGT increase concomitantly to activation of PI3K and MAPK pathways. Co-immunoprecipitation experiments performed upon serum stimulation showed a progressive interaction between OGT and I?-catenin, a major factor in the regulation of cell cycle. OGT expression was also observed in starved HeLa cells reincubated with serum. In these cells, the O-GlcNAcylation status of the I?-catenin-2XFLAG was increased following stimulation. Moreover, I?-catenin-2XFLAG was heavily O-GlcNAcylated in exponentially proliferating HeLa cells when compared to confluent cells. Furthermore, blocking OGT activity using the potent inhibitor Ac-5SGlcNAc prevented serum-stimulated cyclin D1 synthesis and slightly delayed cell proliferation. At last, interfering with OGT expression (siOGT) blocked cyclin D1 expression and decreased PI3K and MAPK activation. Together, our data indicate that expression and catalytic activity of OGT are necessary and essential for G0/G1 transition.

Author List

Olivier-Van Stichelen S, Drougat L, Dehennaut V, El Yazidi-Belkoura I, Guinez C, Mir AM, Michalski JC, Vercoutter-Edouart AS, Lefebvre T

Author

Stephanie Olivier-Van Stichelen PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin