Title : Extensive crosstalk between O-GlcNAcylation and phosphorylation regulates cytokinesis
Abstract :
- Like phosphorylation, the addition of O-linked beta-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
Output (sent_index, trigger,
protein,
sugar,
site):
- 3. sites, , proteins, sites, -
- 9. proteins, , proteins, O-GlcNAcylation, -
Output(Part-Of) (sent_index,
protein,
site):
- 1. proteins, serine and threonine residues
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):