In response to different environmental cues, nuclear and cytoplasmic proteins are posttranslationally modified on serine and threonine residues by the monosaccharide O-GlcNAc, altering protein function. To date, more than 600 proteins have been identified as GlcNAcylated. These proteins belong to a wide range of functional classes, including but not limited to: transcriptional machinery, signaling molecules, scaffolding proteins, trafficking proteins, and metabolic enzymes. However, in mammals, only a single gene encodes O-GlcNAc transferase, the enzyme that catalyzes protein GlcNAcylation. As a result, the mechanisms governing O-GlcNAc transferase's context-dependent substrate selectivity are unclear. In this work, we show that: (1) during glucose deprivation in murine neuroblastoma cells, O-GlcNAc transferase is activated by AMP-activated protein kinase and p38 MAPK signaling pathways, (2) during glucose deprivation, p38 MAPK interacts with O-GlcNAc transferase and targets it to GlcNAcylate neurofilament H, altering its biochemical solubility, and (3) Myosin phosphatase targeting subunit 1 interacts with O-GlcNAc transferase and targets it to GlcNAcylate a number of proteins in vivo and in vitro. Altogether, these data demonstrate that O-GlcNAc transferase's transiently interacting proteins act as adaptor or targeting molecules, dictating its substrate specificity in a context-regulated fashion. Thus, the work presented here represents an important advance in the understanding of O-GlcNAc transferase regulation and function.It will be very interesting to see if more of these proteins serve functional roles as OGT recruitment factors, helping to define ... containing CARM1 cDNA from Dr. Michael R. Stallcup (University of Southern California, Los Angeles, California).
|Title||:||Insights Into the Regulation of O-GlcNAc Transferase and Protein GlcNAcylation|
|Publisher||:||ProQuest - 2009|