N-glycans in cell survival and death: cross-talk between glycosyltransferases.
Asparagine-linked (N-linked) protein glycosylation is one of the most important protein modifications. N-glycans with "high mannose", "hybrid", or "complex" type sugar chains participate in a multitude of cellular processes. These include cell-cell/cell-matrix/receptor-ligand interaction, cell signaling/growth and differentiation, to name a few. Many diseases such as disorders of blood clotting, congenital disorder of glycosylation, diseases of blood vessels, cancer, neo-vascularization, i.e., angiogenesis essential for breast and other solid tumor progression and metastasis are associated with N-glycan expression. Biosynthesis of N-glycans requires multiple steps and multiple cellular compartments. Following transcription and translation the proteins migrate to the endoplasmic reticulum (ER) lumen to acquire glycan chain(s) with a defined glycoform, i.e., a tetradecasaccharide. These are further modified, i.e., edited in ER lumen and in Golgi prior to moving to their respective destinations. The tetradecasaccharide is pre-assembled on a poly-isoprenoid lipid called dolichol, and becomes an essential component of the supply chain. Therefore, dolichol cycle synthesizing the lipid-linked oligosaccharide (LLO) is a hallmark for all N-linked glycoproteins. It is expected that there is a great deal of cross-talk between the participating glycosyltransferases and any missed step would express defective N-glycans that could have fatal consequences. The positive impact of the structurally altered N-glycans could lead to discovery of an N-glycan signature for a disease and/or help developing glycotherapeutic treating cancer or other human diseases. The purpose of this review is to identify the gaps of N-glycan biology and help developing appropriate technology for biomedical applications. This article is part of a Special Issue entitled Glycoproteomics.
Department of Biochemistry, School of Medicine, University of Puerto Rico, Medical Sciences Campus, San Juan, PR 00936-5067. dipak.banerjee@upr.edu
Dipak K
DK
Banerjee
D000818:Animals; D016923:Cell Death; D049109:Cell Proliferation; D002470:Cell Survival; D006023:Glycoproteins / Q000096:biosynthesis / Q000378:metabolism*; D016695:Glycosyltransferases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000502:physiology; D011134:Polysaccharides / Q000378:metabolism* / Q000502:physiology*
D006023:Glycoproteins; D011134:Polysaccharides; D016695:Glycosyltransferases