O-GlcNAcylation in tumorigenesis and its implications for cancer therapy
Dize Zhang, Yihang Qi, Hiroyuki Inuzuka, Jing Liu, Wenyi Wei
Abstract
O-linked N-acetylglucosaminylation (O-GlcNAcylation) is a dynamic and reversible posttranslational modification that targets serine and threonine residues in a variety of proteins. Uridine diphospho-N-acetylglucosamine, which is synthesized from glucose via the hexosamine biosynthesis pathway, is the major donor of this modification. O-GlcNAc transferase is the sole enzyme that transfers GlcNAc onto protein substrates, while O-GlcNAcase is responsible for removing this modification. O-GlcNAcylation plays an important role in tumorigenesis and progression through the modification of specific protein substrates. In this review, we discuss the tumor-related biological functions of O-GlcNAcylation and summarize the recent progress in the development of pharmaceutical options to manipulate the O-GlcNAcylation of specific proteins as potential anticancer therapies.