Core2 O-Glycan Structure Is Essential for the Cell Surface Expression of Sucrase Isomaltase and Dipeptidyl Peptidase-IV during Intestinal Cell Differentiation

Lee, Seung Ho; Yu, Shin‐Yi; Nakayama, Jun; Khoo, Kay‐Hooi; Stone, Erica L.; Marth, Jamey D.; Fukuda, Minoru

doi:10.1074/jbc.m110.162735

Cited by 24 publications

(20 citation statements)

References 41 publications

(40 reference statements)

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“…The polarized distribution of surface 35 S-labeled MUC1-22TR, Tac, and chimeras observed at 120 min of chase (Figs. 2 and 3) also reflects the steady state expression of these proteins when their surface expression is analyzed by confocal immunofluorescence microscopy (Fig.…”

Section: The Signal For Apical Targeting Is Within the Muc1mentioning

confidence: 99%

Core-glycosylated Mucin-like Repeats from MUC1 Are an Apical Targeting Signal

Kinlough

Poland

Gendler

et al. 2011

Journal of Biological Chemistry

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Background: MUC1 apical delivery in polarized MDCK cells employs a path used by proteins with glycan-dependent targeting signals. Results: Core O-glycans on mucin-like repeats of MUC1 act as an apical targeting signal. Conclusion: MUC1 apical targeting is O-glycan-dependent.Significance: We have identified a specific sequence with a post-translational modification that can direct apical delivery of MUC1 or a reporter protein.

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Section: The Signal For Apical Targeting Is Within the Muc1mentioning

confidence: 99%

Core-glycosylated Mucin-like Repeats from MUC1 Are an Apical Targeting Signal

Kinlough

Poland

Gendler

et al. 2011

Journal of Biological Chemistry

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“…x O-linked glycan 5 at a specific N-terminal Thr residue of PSGL1 (Thr-57 in human or Thr-58 in murine PSGL1 (72,73)). The targeted biosynthesis of this O-glycan structure at this site is not understood; however, in the ppGalNAc T1 knock-out mouse PSGL1 is significantly reduced (74).…”

Section: Correlation Of Charged Residue Enhancement Values With Transmentioning

confidence: 99%

“…Consequently, glycoproteins containing O-glycosylated mucin domains function in the protection of the cell surface, the modulation of cell-cell interactions, in the inflammatory and immune response, in metastasis and tumorigenesis, and in protein sorting, targeting, and turnover (for examples see Refs. [1][2][3][4][5]. It is also likely that such O-glycosylated domains may further present a molecular code for the specific recognition of additional binding partners, enzymes, or even other glycosyltransferases.…”

mentioning

confidence: 99%

“…Mucin-type protein O-glycosylation is initiated in the Golgi compartment by the transfer of ␣-GalNAc, from UDPGalNAc, 5 to Ser and Thr residues of polypeptide acceptors by the large family (ϳ20) of UDP-GalNAc:polypeptide ␣-Nacetylgalactosaminyltransferases (ppGalNAc Ts). By subsequent action of a series of specific glycosyltransferases, the O-linked glycan can be further elongated to produce a vast array of glycan structures (14).…”

mentioning

confidence: 99%

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Emerging Paradigms for the Initiation of Mucin-type Protein O-Glycosylation by the Polypeptide GalNAc Transferase Family of Glycosyltransferases

Gerken¹,

Jamison²,

Perrine³

et al. 2011

Journal of Biological Chemistry

139

160

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Mammalian mucin-type O-glycosylation is initiated by a large family of ϳ20 UDP-GalNAc:polypeptide ␣-N-acetylgalactosaminyltransferases (ppGalNAc Ts) that transfer ␣-GalNAc from UDP-GalNAc to Ser and Thr residues of polypeptide acceptors. Characterizing the peptide substrate specificity of each isoform is critical to understanding their properties, biological roles, and significance. Presently, only the specificities of ppGalNAc T1, T2, and T10 and the fly orthologues of T1 and T2 have been systematically characterized utilizing random peptide substrates. We now extend these studies to ppGalNAc T3, T5, and T12, transferases variously associated with human disease. Our results reveal several common features; the most striking is the similar pattern of enhancements for the three residues C-terminal to the site of glycosylation for those transferases that contain a common conserved Trp. In contrast, residues N-terminal to the site of glycosylation show a wide range of isoform-specific enhancements, with elevated preferences for Pro, Val, and Tyr being the most common at the ؊1 position. Further analysis reveals that the ratio of positive (Arg, Lys, and His) to negative (Asp and Glu) charged residue enhancements varied among transferases, thus further modulating substrate preference in an isoform-specific manner. By utilizing the obtained transferase-specific preferences, the glycosylation patterns of the ppGalNAc Ts against a series of peptide substrates could roughly be reproduced, demonstrating the potential for predicting isoform-specific glycosylation. We conclude that each ppGalNAc T isoform may be uniquely sensitive to peptide sequence and overall charge, which together dictates the substrate sites that will be glycosylated.Mucin-type O-glycosylation is one of the most common post-translational modifications of secreted and membrane-associated proteins. Glycoproteins containing O-glycosylated mucin domains serve many important biological roles chiefly because of their unique biophysical and structural properties that include an extended peptide conformation and robust resistance to proteases. Consequently, glycoproteins containing O-glycosylated mucin domains function in the protection of the cell surface, the modulation of cell-cell interactions, in the inflammatory and immune response, in metastasis and tumorigenesis, and in protein sorting, targeting, and turnover (for examples see Refs.

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“…Biosynthesis of oligosaccharides on glycoproteins is performed in concert by several glycosyltransferases; GCNT1 is one of the glycosyltransferases that forms the core 2 O-glycans on the surface of lymphocytes and various cancer cells [13,14,26,27]. It is noteworthy that the present study clearly demonstrated that immunohistochemical status of GCNT1 expression on prostate biopsy specimen 11 closely related to extra-prostatic extension, lymph node metastasis of PCa (Table 2).…”

Section: Discussionmentioning

confidence: 51%

Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness

Sato

Yoneyama

Tobisawa

et al. 2016

Biochemical and Biophysical Research Communications

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Introduction: To avoid over-treatment of early stage prostate cancer (PCa), predictive biomarkers for PCa aggressiveness which can be obtained during pre-treatment evaluation are essential. Core 2 β-1, 6-N-acetylglucosaminyl-transferase-1 (GCNT1) is a key enzyme that forms core 2 branched O-glycans, the expression of which is associated with aggressive potential of prostate cancer. We examined whether GCNT1 expression in prostate biopsy specimen can predict cancer recurrence after radical prostatectomy for the patients with with PCa. We then investigated molecular background for aggressive malignant potential mediated by GCNT1 expression.Methods: Paraffin-embedded PCa biopsy specimens were immunohisto-chemically tested for GCNT1 expression using an anti-GCNT1 monoclonal antibody. We also examined the role of GCNT1 in PCa progression using cell lines which express high or low levels of GCNT1.Results: GCNT1 expression correlated with D' Amico's recurrence risk classification. The GCNT1-positive rate in organ confined PCa was significantly lower than that in PCa with extra-prostatic extension. GCNT1-negative tumors were associated with significantly better prostate-specific antigen (PSA)-free survival compared with GCNT1-positive tumors. Multivariate analysis revealed that GCNT1 expression status was an independent risk factor for PSA recurrence after radical prostatectomy. Subsequent basic study revealed that GCNT1-over-expressing cells produced a significantly larger amount of growth factors when co-cultured with prostate stromal cells compared with GCNT1-knocked down cells and formed larger tumors. Conclusions: GCNT1 expression in prostate biopsy specimen is a significant and independent predictor of recurrence after radical prostatectomy, which can be used in pre-treatment decision making for the patient. Further validation study is necessary to establish clinical implication of GCNT1 in management of PCa.3

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Core2 O-Glycan Structure Is Essential for the Cell Surface Expression of Sucrase Isomaltase and Dipeptidyl Peptidase-IV during Intestinal Cell Differentiation

Cited by 24 publications

References 41 publications

Core-glycosylated Mucin-like Repeats from MUC1 Are an Apical Targeting Signal

Core-glycosylated Mucin-like Repeats from MUC1 Are an Apical Targeting Signal

Emerging Paradigms for the Initiation of Mucin-type Protein O-Glycosylation by the Polypeptide GalNAc Transferase Family of Glycosyltransferases

Core 2 β-1, 6-N-acetylglucosaminyltransferase-1 expression in prostate biopsy specimen is an indicator of prostate cancer aggressiveness

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