Fucosylation

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Fucosylation is the process of adding fucose sugar units to a molecule. It is a type of glycosylation. [1]

It is important clinically, [2] [3] and high levels of fucosylation have been reported in cancer. [4] [5] In cancer and inflammation there are significant changes in the expression of fucosylated molecules. Therefore, antibodies and lectins that are able to recognize cancer associated fucosylated oligosaccharides have been used as tumor markers in oncology. [6]

It is performed by fucosyltransferase enzymes. [1]

Fucosylation has been observed in vertebrates, invertebrates, plants, bacteria, and fungi. It has a role in cellular adhesion and immune regulation. Fucosylation inhibition applications are being explored for a range of clinical application including some associated with sickle cell disease, rheumatoid arthritis, tumor inhibition, and chemotherapy improvements. [7] Recent studies on melanoma patient specimens indicated that melanoma fucosylation and fucosylated HLA-DRB1 are associated with anti-programmed cell death protein 1 (PD1) responder status, pointing to the potential use of melanoma fucosylation as a method for immunotherapy patient stratification. [8] Moreover, it has been reported that fucosylation is an important regulator of anti-tumor immunity and L-fucose can be used as a potent tool for increasing immunotherapy efficacy in melanoma. [8]

Fucosylation can help with immune response when a foreign pathogen is introduced in the body. Rapid fucosylation can occur in the epithelial lining of the small intestine as a protective mechanism to support the body’s symbiotic gut bacteria. This may regulate the bacterial genes responsible for quorum sensing or virulence, thus resulting in an increased tolerance of the infection. [9]

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References

  1. 1 2 "Fucosylation in prokaryotes and eukaryotes". academic.oup.com. Retrieved 2 November 2023.
  2. ↑ Ma, B.; Simala-Grant, J. L.; Taylor, D. E. (2006). "Fucosylation in prokaryotes and eukaryotes". Glycobiology. 16 (12): 158R–184R. doi: 10.1093/glycob/cwl040 . PMID   16973733.
  3. ↑ Miyoshi, E.; Moriwaki, K.; Nakagawa, T. (2007). "Biological Function of Fucosylation in Cancer Biology". Journal of Biochemistry. 143 (6): 725–729. doi:10.1093/jb/mvn011. PMID   18218651.
  4. ↑ Miyoshi, Eiji (2008). "Fucosylation and Cancer". Experimental Glycoscience. Springer. pp. 235–7. doi:10.1007/978-4-431-77922-3_57. ISBN   978-4-431-77921-6.
  5. ↑ Nakagawa, T.; Uozumi, N; Nakano, M; Mizuno-Horikawa, Y; Okuyama, N; Taguchi, T; Gu, J; Kondo, A; et al. (2006). "Fucosylation of N-Glycans Regulates the Secretion of Hepatic Glycoproteins into Bile Ducts". Journal of Biological Chemistry. 281 (40): 29797–29806. doi: 10.1074/jbc.M605697200 . PMID   16899455.
  6. ↑ Moriwaki, Kenta (2010). "Fucosylation and gastrointestinal cancer". World Journal of Hepatology. 2 (4): 151–161. doi: 10.4254/wjh.v2.i4.151 . PMC   2999278 . PMID   21160988.
  7. ↑ Li J, Hsu HC, Mountz JD, Allen JG (May 2018). "Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and Diseases". Cell Chem Biol. 25 (5): 499–512. doi: 10.1016/j.chembiol.2018.02.005 . PMID   29526711.
  8. 1 2 Lester, Daniel K.; Burton, Chase; Gardner, Alycia; Innamarato, Patrick; Kodumudi, Krithika; Liu, Qian; Adhikari, Emma; Ming, Qianqian; Williamson, Daniel B.; Frederick, Dennie T.; Sharova, Tatyana; White, Michael G.; Markowitz, Joseph; Cao, Biwei; Nguyen, Jonathan (February 2023). "Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy". Nature Cancer. 4 (2): 222–239. doi:10.1038/s43018-022-00506-7. ISSN   2662-1347. PMC   9970875 . PMID   36690875.
  9. ↑ Pickard, Joseph M.; Maurice, Corinne F.; Kinnebrew, Melissa A.; Abt, Michael C.; Schenten, Dominik; Golovkina, Tatyana V.; Bogatyrev, Said R.; Ismagilov, Rustem F.; Pamer, Eric G.; Turnbaugh, Peter J.; Chervonsky, Alexander V. (October 2014). "Rapid fucosylation of intestinal epithelium sustains host–commensal symbiosis in sickness". Nature. 514 (7524): 638–641. Bibcode:2014Natur.514..638P. doi:10.1038/nature13823. PMC   4214913 . PMID   25274297.
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