A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase

Ju, Tongzhong; Cummings, Richard D.

doi:10.1073/pnas.262438199

Cited by 441 publications

(446 citation statements)

References 33 publications

Supporting

Mentioning

423

Contrasting

Unclassified

Order By: Relevance

“…Second, GnT-III may associate with some other molecules, which define the specificities for protein or peptide substrates. Several studies have shown that the glycosyltransferase complex formation may play a crucial role in the determination of both activity and substrate specificity [35,36]. Third, each glycosyltransferase may have its own pathway to operate glycosylation in Golgi apparatus.…”

Section: Roles Of N-glycosylation On α5β1 Integrinmentioning

confidence: 99%

Potential roles of N-glycosylation in cell adhesion

Isaji

et al. 2012

Glycoconj J

131

View full text Add to dashboard Cite

The functional units of cell adhesion are typically multiprotein complexes made up of three general classes of proteins; the adhesion receptors, the cell-extracellular matrix (ECM) proteins, and the cytoplasmic plaque/peripheral membrane proteins. The cell adhesion receptors are usually transmembrane glycoproteins (for example E-cadherin and integrin) that mediate binding at the extracellular surface and determine the specificity of cell-cell and cell-ECM recognition. E-cadherin-mediated cell-cell adhesion can be both temporally and spatially regulated during development, and represents a key step in the acquisition of the invasive phenotype for many tumors. On the other hand, integrin-mediated cell-ECM interactions play important roles in cytoskeleton organization and in the transduction of intracellular signals to regulate various processes such as proliferation, differentiation and cell migration. ECM proteins are typically large glycoproteins, including the collagens, fibronectins, laminins, and proteoglycans that assemble into fibrils or other complex macromolecular arrays. The most of these adhesive proteins are glycosylated. Here, we focus mainly on the modification of N-glycans of integrins and laminin-332, and a mutual regulation between cell adhesion and bisected N-glycan expression, to address the important roles of N-glycans in cell adhesion.

show abstract

Section: Roles Of N-glycosylation On α5β1 Integrinmentioning

confidence: 99%

Potential roles of N-glycosylation in cell adhesion

Isaji

et al. 2012

Glycoconj J

131

View full text Add to dashboard Cite

show abstract

“…For further elongation, T‐synthase (core 1 β1,3‐galactosyltransferase) is the key enzyme during the O‐glycosylation process 14. Interestingly, the expression and activity of T‐synthase require an endoplasmic reticulum(ER)‐resident molecular chaperone named Cosmc 15, 16, 17. Knockout of either T‐synthase or Cosmc in mice causes Tn expression in vivo 18, 19, 20.…”

Section: Introductionmentioning

confidence: 99%

“…Overall, T‐synthase, Cosmc and C3GnT are essential for complete O‐glycosylation in colonic tissues. Accordingly, aberrant O‐glycosylation in colonic tissues, characterized by Tn antigen exposure, has been suggested to arise from disturbances in the expression and activity levels of T‐synthase, Cosmc and/or C3GnT 17, 22, 23, 24, 25. However, it is not known whether or how aberrant O‐glycosylation may contribute to the development and progression of CRC.…”

Section: Introductionmentioning

confidence: 99%

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Jiang

Liu

et al. 2018

J Cellular Molecular Medi

View full text Add to dashboard Cite

Aberrant O‐glycosylation is frequently observed in colorectal cancer (CRC) patients, but it is unclear if it contributes intrinsically to tumorigenesis. Here, we investigated the biological consequences of aberrant O‐glycosylation in CRC. We first detected the expression profile of Tn antigen in a serial of human CRC tissues and then explored the genetic and biosynthetic mechanisms. Moreover, we used a human CRC cell line (LS174T), which express Tn antigen, to assess whether aberrant O‐glycosylation can directly promote oncogenic properties. It showed that Tn antigen was detected in around 86% human primary and metastatic CRC tissues. Bio‐functional investigations showed that T‐synthase and Cosmc were both impaired in cancer tissues. A further analysis detected an occurrence of hypermethylation of Cosmc gene, which possibly caused its loss‐of‐function and a consequent inactive T‐synthase. Transfection of LS174T cells with WT Cosmc restored mature O‐glycosylation, which subsequently down‐regulated cancer cell proliferation, migration and apoptotic‐resistant ability. Significantly, the expression of MUC2, a heavily O‐glycosylated glycoprotein that plays an essential role in intestinal function, was uniformly reduced in human CRC tissues as well as in LS174T cells. These data suggest that aberrant O‐glycosylation contributes to the development of CRC through direct induction of oncogenic properties in cancer cells.

show abstract

“…T-synthase (C1␤3Gal-T) forms a complex with core 1 ␤3GalT-specific molecular chaperone, which functions as a specific chaperone. Core 1 ␤3GalT-specific molecular chaperone is essential for the T-synthase activity and synthesizing T-antigen (42). Actually, core 1 ␤3GalT-specific molecular chaperone is a factor responsible for Tn syndrome, a genetic disease involving a deficiency in T-antigen but no defect in T-synthase (43).…”

Section: Discussionmentioning

confidence: 99%

Specific Enzyme Complex of β-1,4-Galactosyltransferase-II and Glucuronyltransferase-P Facilitates Biosynthesis of N-linked Human Natural Killer-1 (HNK-1) Carbohydrate

Kouno

Kizuka

Nakagawa

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Human natural killer-1 (HNK-1) carbohydrate is highly expressed in the nervous system and is involved in synaptic plasticity and dendritic spine maturation. This unique carbohydrate, consisting of a sulfated trisaccharide (HSO 3 -3GlcA␤1-3Gal␤1-4GlcNAc-), is biosynthesized by the successive actions of ␤-1,4-galactosyltransferase (␤4GalT), glucuronyltransferase (GlcAT-P and GlcAT-S), and sulfotransferase (HNK-1ST). A previous study showed that mice lacking ␤4GalT-II, one of seven ␤4GalTs, exhibited a dramatic loss of HNK-1 expression in the brain, although ␤4GalT-I-deficient mice did not. Here, we investigated the underlying molecular mechanism of the regulation of HNK-1 expression. First, focusing on a major HNK-1 carrier, neural cell adhesion molecule, we found that reduced expression of an N-linked HNK-1 carbohydrate caused by a deficiency of ␤4GalT-II is not likely due to a general loss of the ␤1,4-galactose residue as an acceptor for GlcAT-P. Instead, we demonstrated by co-immunoprecipitation and endoplasmic reticulum-retention analyses using Neuro2a (N2a) cells that ␤4GalT-II physically and specifically associates with GlcAT-P. In addition, we revealed by pulldown assay that Golgi luminal domains of ␤4GalT-II and GlcAT-P are sufficient for the complex to form. With an in vitro assay system, we produced the evidence that the kinetic efficiency k cat /K m of GlcAT-P in the presence of ␤4GalT-II was increased about 2.5-fold compared with that in the absence of ␤4GalT-II. Finally, we showed that co-expression of ␤4GalT-II and GlcAT-P increased HNK-1 expression on various glycoproteins in N2a cells, including neural cell adhesion molecule. These results indicate that the specific enzyme complex of ␤4GalT-II with GlcAT-P plays an important role in the biosynthesis of HNK-1 carbohydrate.

show abstract

A unique molecular chaperone Cosmc required for activity of the mammalian core 1 β3-galactosyltransferase

Cited by 441 publications

References 33 publications

Potential roles of N-glycosylation in cell adhesion

Potential roles of N-glycosylation in cell adhesion

Aberrant O‐glycosylation contributes to tumorigenesis in human colorectal cancer

Specific Enzyme Complex of β-1,4-Galactosyltransferase-II and Glucuronyltransferase-P Facilitates Biosynthesis of N-linked Human Natural Killer-1 (HNK-1) Carbohydrate

Contact Info

Product

Resources

About