The regulation of Aurora Kinase B by O‐GlcNAcylation

Abstract

Post‐translational modifications are essential in regulating the function, stability, and localization of proteins. The O‐GlcNAc modification is the attachment of a single N‐acetylglucosamine moiety to serine and threonine residues on nuclear and cytoplasmic proteins. This dynamic modification is processed by the enzymes O‐GlcNAc transferase (O‐GlcNAc addition) or O‐GlcNAcase (O‐GlcNAc removal). The O‐GlcNAc signaling system interacts with and alters other signaling cascades, such as phosphorylation. Previously, we have demonstrated that O‐GlcNAc transferase (OGT) and O‐GlcNAcase (OGA) interact with Aurora Kinase B, a kinase essential in regulating mitosis. Our objective in this study is to determine how Aurora Kinase B is regulated by the O‐GlcNAc signaling system. We employed HeLa cells with either OGT or OGA gain or loss of function and discovered that there is a reduction in the protein levels of Aurora Kinase B and its’ binding partner INCENP. Next, we measured a downstream substrate of Aurora Kinase B, phosphorylation of serine 10 on histone H3, and saw a marked decrease in phosphorylation under all cellular conditions with altered O‐GlcNAcylation. These findings suggest that O‐GlcNAc signaling system plays a role in regulating the activity of Aurora Kinase B through multiple cellular processes, and that aberrant O‐GlcNAcylation can alter Aurora Kinase B signaling and mitotic progression.