Intracellular protein O-GlcNAc modification integrates nutrient status with transcriptional and metabolic regulation.
The inducible, nutrient-sensitive posttranslational modification of protein Ser/Thr residues with O-linked β-N-acetylglucosamine (O-GlcNAc) occurs on histones, transcriptional regulators, metabolic enzymes, oncogenes, tumor suppressors, and many critical intermediates of growth factor signaling. Cycling of O-GlcNAc modification on and off of protein substrates is catalyzed by the actions of O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. To date, there are less than 150 publications addressing the role of O-GlcNAc modification in cancer and over half were published in the last 2 years. These studies have clearly established that increased expression of OGT and hyper-O-GlcNAcylation is common to human cancers of breast, prostate, colon, lung, and pancreas. Furthermore, attenuating OGT activity reduces tumor growth in vitro and metastasis in vivo. This chapter discusses the structure and function of the O-GlcNAc cycling enzymes, mechanisms by which protein O-GlcNAc modification sense changes in nutrient status, the influence of O-GlcNAc cycling enzymes on glucose metabolism, and provides an overview of recent observations regarding the role of O-GlcNAcylation in cancer.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, USA; Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Alexis K
AK
Nagel
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina, USA; Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA. Electronic address: ballle@musc.edu.
Lauren E
LE
Ball
D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D057890:Epigenomics; D005502:Food; D006031:Glycosylation; D006801:Humans; D053858:Metabolic Networks and Pathways; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D017351:N-Acetylglucosaminyltransferases; C449880:O-GlcNAc transferase; D000117:Acetylglucosamine
Cancer; Hexosamine biosynthetic pathway; MGEA5; Metabolic reprogramming; O-GlcNAc modification; O-GlcNAc transferase; O-GlcNAcase