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Keywords = CDP-glycerol (CDP-Gro)

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15 pages, 3115 KB  
Article
Cancer Malignancy Is Correlated with Upregulation of PCYT2-Mediated Glycerol Phosphate Modification of α-Dystroglycan
by Fumiko Umezawa, Makoto Natsume, Shigeki Fukusada, Kazuki Nakajima, Fumiya Yamasaki, Hiroto Kawashima, Chu-Wei Kuo, Kay-Hooi Khoo, Takaya Shimura, Hirokazu Yagi and Koichi Kato
Int. J. Mol. Sci. 2022, 23(12), 6662; https://doi.org/10.3390/ijms23126662 - 15 Jun 2022
Cited by 12 | Viewed by 4600
Abstract
The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part [...] Read more.
The dystrophin–glycoprotein complex connects the cytoskeleton with base membrane components such as laminin through unique O-glycans displayed on α-dystroglycan (α-DG). Genetic impairment of elongation of these glycans causes congenital muscular dystrophies. We previously identified that glycerol phosphate (GroP) can cap the core part of the α-DG O-glycans and terminate their further elongation. This study examined the possible roles of the GroP modification in cancer malignancy, focusing on colorectal cancer. We found that the GroP modification critically depends on PCYT2, which serves as cytidine 5′-diphosphate-glycerol (CDP-Gro) synthase. Furthermore, we identified a significant positive correlation between cancer progression and GroP modification, which also correlated positively with PCYT2 expression. Moreover, we demonstrate that GroP modification promotes the migration of cancer cells. Based on these findings, we propose that the GroP modification by PCYT2 disrupts the glycan-mediated cell adhesion to the extracellular matrix and thereby enhances cancer metastasis. Thus, the present study suggests the possibility of novel approaches for cancer treatment by targeting the PCYT2-mediated GroP modification. Full article
(This article belongs to the Special Issue New Insights on Roles of Glycoconjugates in Health and Diseases)
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14 pages, 1464 KB  
Review
Biosynthetic Mechanisms and Biological Significance of Glycerol Phosphate-Containing Glycan in Mammals
by Rieko Imae, Hiroshi Manya and Tamao Endo
Molecules 2021, 26(21), 6675; https://doi.org/10.3390/molecules26216675 - 4 Nov 2021
Cited by 4 | Viewed by 3759
Abstract
Bacteria contain glycerol phosphate (GroP)-containing glycans, which are important constituents of cell-surface glycopolymers such as the teichoic acids of Gram-positive bacterial cell walls. These glycopolymers comprising GroP play crucial roles in bacterial physiology and virulence. Recently, the first identification of a GroP-containing glycan [...] Read more.
Bacteria contain glycerol phosphate (GroP)-containing glycans, which are important constituents of cell-surface glycopolymers such as the teichoic acids of Gram-positive bacterial cell walls. These glycopolymers comprising GroP play crucial roles in bacterial physiology and virulence. Recently, the first identification of a GroP-containing glycan in mammals was reported as a variant form of O-mannosyl glycan on α-dystroglycan (α-DG). However, the biological significance of such GroP modification remains largely unknown. In this review, we provide an overview of this new discovery of GroP-containing glycan in mammals and then outline the recent progress in elucidating the biosynthetic mechanisms of GroP-containing glycans on α-DG. In addition, we discuss the potential biological role of GroP modification along with the challenges and prospects for further research. The progress in this newly identified glycan modification will provide insights into the phylogenetic implications of glycan. Full article
(This article belongs to the Special Issue New Insights into Protein Glycosylation)
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