scholarly journals The Diverse Contributions of Fucose Linkages in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1241 ◽  
Author(s):  
Tyler S. Keeley ◽  
Shengyu Yang ◽  
Eric Lau

Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O’- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.

2021 ◽  
Author(s):  
Pardis Pakshir

One of the crucial key targets in treatment of diseases are cell surface proteins, such as receptor complexes, and their associated signaling pathways. The Fc receptor is one of the most important phagocytic receptors of the cells of immune system. The ligand of the Fc gamma receptor is immunoglobulin G (IgG), which triggers the engulfment of foreign molecules coated by antibodies by a process called phagocytosis. A Specialized subset of cells including macrophages engulfs foreign particles by the Fc receptor. Another phagocytic receptor of macrophages is the CD36 receptor, which binds the ligand oxLDL and is known to be involved in the development of atherosclerotic lesions in the arteries. A few members of the Tetraspanin proteins have been found to be associated with theses receptors in macrophages. Tetraspanins may act as “molecular facilitators” grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. There is a significant amount of research done on the receptors of the surface of macrophages, however, the proteins associated with these receptors, their potential signaling pathways and the mechanisms involved are not yet fully understood. This thesis aims to investigate the presence and potential functional role of the specific Tetraspanin isoforms in Fc and CD36 mediated phagocytosis. Silencing RNA, quantitative assays of phagocytosis, and laser scanning confocal microscopy were used to test the phagocytic efficiency of macrophages in IgG and oxLDL mediated phagocytosis. Understanding the regulatory roles of Tetraspanins can provide insight into various immune diseases.


2018 ◽  
Vol 399 (12) ◽  
pp. 1353-1361 ◽  
Author(s):  
Katarina Hočevar ◽  
Jan Potempa ◽  
Boris Turk

Abstract Gingipains are extracellular cysteine proteases of the oral pathogen Porphyromonas gingivalis and are its most potent virulence factors. They can degrade a great variety of host proteins, thereby helping the bacterium to evade the host immune response, deregulate signaling pathways, trigger anoikis and, finally, cause tissue destruction. Host cell-surface proteins targeted by gingipains are the main focus of this review and span three groups of substrates: immune-regulatory proteins, signaling pathways regulators and adhesion molecules. The analysis of published data revealed that gingipains predominantly inactivate their substrates by cleaving them at one or more sites, or through complete degradation. Sometimes, gingipains were even found to initially shed their membrane substrates, but this was mostly just the first step in the degradation of cell-surface proteins.


2021 ◽  
Author(s):  
Anna Cioce ◽  
Beatriz Calle ◽  
Andrea Marchesi ◽  
Ganka Bineva-Todd ◽  
Helen Flynn ◽  
...  

Interactions between cells fundamentally impact biological processes. In cancer development, such interactions define key stages of disease that cannot be adequately recapitulated in cell monoculture. Complex co-culture studies have been key to unraveling the complexity of these processes, usually by sorting cells and transcriptome or bulk proteome analyses. However, these methods invariably lead to sample loss and do not capture aberrant glycosylation as an important corollary of cancer formation. Here, we report the development of Bio-Orthogonal Cell line-specific Tagging of Glycoproteins (BOCTAG). Cells are equipped with a biosynthetic AND gate that uses bioorthogonally tagged sugars to generate glycosylation precursors. The cellular glycosylation machinery then introduces bioorthogonal tags into glycoproteins exclusively in cell lines expressing the enzymes of the biosynthetic AND gate. Modification with clickable reporter moieties allows for imaging or enrichment with mass spectrometry-proteomics in a cell-specific fashion. Making use of glycans as a property of most cell surface proteins, we use BOCTAG as an efficient means for cell-specific protein tracing.


2021 ◽  
Author(s):  
Pardis Pakshir

One of the crucial key targets in treatment of diseases are cell surface proteins, such as receptor complexes, and their associated signaling pathways. The Fc receptor is one of the most important phagocytic receptors of the cells of immune system. The ligand of the Fc gamma receptor is immunoglobulin G (IgG), which triggers the engulfment of foreign molecules coated by antibodies by a process called phagocytosis. A Specialized subset of cells including macrophages engulfs foreign particles by the Fc receptor. Another phagocytic receptor of macrophages is the CD36 receptor, which binds the ligand oxLDL and is known to be involved in the development of atherosclerotic lesions in the arteries. A few members of the Tetraspanin proteins have been found to be associated with theses receptors in macrophages. Tetraspanins may act as “molecular facilitators” grouping specific cell-surface proteins and thus increasing the formation and stability of functional signaling complexes. There is a significant amount of research done on the receptors of the surface of macrophages, however, the proteins associated with these receptors, their potential signaling pathways and the mechanisms involved are not yet fully understood. This thesis aims to investigate the presence and potential functional role of the specific Tetraspanin isoforms in Fc and CD36 mediated phagocytosis. Silencing RNA, quantitative assays of phagocytosis, and laser scanning confocal microscopy were used to test the phagocytic efficiency of macrophages in IgG and oxLDL mediated phagocytosis. Understanding the regulatory roles of Tetraspanins can provide insight into various immune diseases.


Author(s):  
Watt W. Webb

Plasma membrane heterogeneity is implicit in the existence of specialized cell surface organelles which are necessary for cellular function; coated pits, post and pre-synaptic terminals, microvillae, caveolae, tight junctions, focal contacts and endothelial polarization are examples. The persistence of these discrete molecular aggregates depends on localized restraint of the constituent molecules within specific domaines in the cell surface by strong intermolecular bonds and/or anchorage to extended cytoskeleton. The observed plasticity of many of organelles and the dynamical modulation of domaines induced by cellular signaling evidence evanescent intermolecular interactions even in conspicuous aggregates. There is also strong evidence that universal restraints on the mobility of cell surface proteins persist virtually everywhere in cell surfaces, not only in the discrete organelles. Diffusion of cell surface proteins is slowed by several orders of magnitude relative to corresponding protein diffusion coefficients in isolated lipid membranes as has been determined by various ensemble average methods of measurement such as fluorescence photobleaching recovery(FPR).


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