Purification and cDNA Cloning of a Human UDP-N-acetyl-α- D-galactosamine:polypeptide N-Acetylgalactosaminyltransferase

White, Thayer; Bennett, Eric; Takio, Koji; Sørensen, Thomas Lund; Bonding, Nina; Clausen, Henrik

doi:10.1074/jbc.270.41.24156

Cited by 195 publications

(162 citation statements)

References 41 publications

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“…The finding that GalNAc-T3 expression was retained more frequently in nonsquamous cell carcinomas (most of which were adenocarcinomas) than in squamous cell carcinomas may reflect tissue specific expression of GalNAc-T3 in organs that contain secretory epithelial glands (Hagen et al, 1993; Homa et al, GalNAc-T3 expression in NSCLCs H Dosaka-Akita et al 1993; White et al, 1995;Bennett et al, 1996). Moreover, in nonsquamous cell carcinomas, decreased expression of GalNAc-T3 was associated with unfavourable prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The initial glycosylation of mucin-type O-linked proteins is catalysed by one of the UDP-N-acetyl-a-D-Galactosamine: polypeptide Nacetylgalactosaminyl transferases (GalNAc-transferase family of enzymes) (Hagen et al, 1993;Homa et al, 1993;Wandall et al, 1997;). Three distinct human GalNAc-transferases, GalNAc-T1, GalNAc-T2, and GalNAc-T3, have been characterised (White et al, 1995;Bennett et al, 1996;Wandall et al, 1997). Recently another 3 homologue enzymes, GalNAc-T4, GalNAc-T5, and GalNAc-T6, have been identified (Bennett et al, 1996(Bennett et al, , 1998(Bennett et al, , 1999Ten Hagen et al, 1998).…”

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confidence: 99%

“…Compared with the expression of GalNAc-T1 and GalNAc-T2, the expression of GalNAc-T3 is highly tissue specific. GalNAc-T3 mRNA has been detected in organs that contain secretory epithelial glands (Hagen et al, 1993;Homa et al, 1993;White et al, 1995;Bennett et al, 1996). It is hypothesised that the differential expression of GalNAc-T3 may affect the specialised functions of glycoproteins produced by normal and malignant cells, and that it is also associated with biological properties of normal and malignant cells (Sutherlin et al, 1997).…”

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N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

et al. 2002

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N-acetylgalactosaminyl transferase-3 (GalNAc-T3) is an enzyme involved in the initial glycosylation of mucin-type O-linked proteins. In the present study, we used immunohistochemistry to examine GalNAc-T3 expression in 215 surgically resected non-small cell lung cancers. We analysed the biological and clinical importance of GalNAc-T3 expression, especially with regard to its potential as a prognostic factor. We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3. Low expression of GalNAc-T3, observed in 93 of 215 tumours (43.4%), was found more frequently in tumours from smokers than those from nonsmokers (P=0.001), in squamous cell carcinomas than nonsquamous cell carcinomas (P50.0001), and in moderately and poorly differentiated tumours than well differentiated tumours (P=0.0002). Multivariate logistic regression analysis showed that an association of low GalNAc-T3 expression with squamous cell carcinomas was the only one significant relationship of GalNAc-T3 expression with various factors (P50.0001). Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003). Patients with low GalNAc-T3 expression survived a significantly shorter time than patients with high GalNAc-T3 expression in 103 pStage I non-small cell lung cancers (5-year survival rates, 58% and 78%, respectively; P=0.02 by log-rank test) as well as in 61 pStage I nonsquamous cell carcinomas (5-year survival rates, 63% and 85%, respectively; P=0.03). Low GalNAc-T3 expression was an unfavourable prognostic factor in pStage I non-small cell lung cancers (hazards ratio, 2.04; P=0.03), and in pStage I nonsquamous cell carcinomas (hazards ratio, 2.70; P=0.03). These results suggest that GalNAc-T3 is a new marker of non-small cell lung cancers with specificity for histology and prognosis.

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N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

et al. 2002

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“…N -acetylgalactosaminyltransferases (GalNAc-Tases) catalyse the first step in the O -glycosylation of mammalian proteins by transferring N -acetyl-D-galactosamine (GalNAc) to peptide substrates. Fifteen distinct members of the mammalian GalNAc-Tases family have been identified and characterized [1-13]. Some of them are widely distributed in various human tissues, but others show tissue-specific distribution.…”

Section: Introductionmentioning

confidence: 99%

N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry

Guo

Wang

et al. 2010

BMC Cancer

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BackgroundThe post-translational modification of proteins, including glycosylation, differs between normal and tumor cells. The UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferases (GalNAc-Tases) family of enzymes regulates the initial steps of mucin O-glycosylation and is responsible for the altered glycosylation state observed in cancer cells. Recently it was found that GalNAc-T14 mRNA is heterogeneously expressed in breast carcinomas compared to normal tissue, however the expression profile of GalNAc-T14 protein in breast carcinomas compared to normal tissue is still unknown. In this study, we assessed the expression profile of GalNAc-T14 protein in malignant and non-malignant breast tissues by immunohistochemistry to evaluate whether GalNAc-T14 might be a potential biomarker for breast cancer.MethodsIn formalin-fixed tissues, the expression level of GalNAc-T14 protein was evaluated by immunohistochemistry assay in breast tissues. Expression profiles were assessed in normal tissues, benign fibroadenomas and several types of carcinomas.ResultsOur results showed that GalNAc-T14 was heterogeneously expressed in breast carcinomas compared to non-malignant tissue. GalNAc-T14 expression was observed in 47/56 (83.9%) carcinoma samples, 7/48 (14.6%) non-malignant breast tissue samples. GalNAc-T14 expression level was associated with histological grade. For this enzyme a significant association with invasive ductal type, mucinous adenocarcinoma and ductal carcinoma in situ (DCIS) type was found.ConclusionOur results provide evidence that GalNAc-T14 may be a potential biomarker for breast cancer by immunohistochemistry. GalNAc-T14 expression level was associated with histological grade. GalNAc-T14 expression can provide new insights about breast cancer glycobiology.

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“…: NP_660335.2] is classified as a member of the ppGalNAc-T family because GALNTL5 possesses highly conserved catalytic domains of pp-GalNAc-T, whereas it uniquely lacks the conserved lectin domain at the C terminus. Thus far, 20 distinct pp-GalNAc-T genes have been identified in the human genome (2,(4)(5)(6). The in vitro enzymatic activities as a glycosyltransferase have been confirmed for 14 members of this family using acceptor peptide substrates (2, 7), but not identified for the other 6 members, including GALNTL5.…”

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A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility

Takasaki

Tachibana

Ogasawara

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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For normal fertilization in mammals, it is important that functionally mature sperm are motile and have a fully formed acrosome. The glycosyltransferase-like gene, human polypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5), belongs to the polypeptide N-acetylgalactosamine-transferase (pp-GalNAc-T) gene family because of its conserved glycosyltransferase domains, but it uniquely truncates the C-terminal domain and is expressed exclusively in human testis. However, glycosyltransferase activity of the human GALNTL5 protein has not been identified by in vitro assay thus far. Using mouse Galntl5 ortholog, we have examined whether GALNTL5 is a functional molecule in spermatogenesis. It was observed that mouse GALNTL5 localizes in the cytoplasm of round spermatids in the region around the acrosome of elongating spermatids, and finally in the neck region of spermatozoa. We attempted to establish Galntl5-deficient mutant mice to investigate the role of Galntl5 in spermiogenesis and found that the heterozygous mutation affected male fertility due to immotile sperm, which is diagnosed as asthenozoospermia, an infertility syndrome in humans. Furthermore, the heterozygous mutation of Galntl5 attenuated glycolytic enzymes required for motility, disrupted protein loading into acrosomes, and caused aberrant localization of the ubiquitin-proteasome system. By comparing the protein compositions of sperm from infertile males, we found a deletion mutation of the exon of human GALNTL5 gene in a patient with asthenozoospermia. This strongly suggests that the genetic mutation of human GALNTL5 results in male infertility with the reduction of sperm motility and that GALNTL5 is a functional molecule essential for mammalian sperm formation.

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Purification and cDNA Cloning of a Human UDP-N-acetyl-α- D-galactosamine:polypeptide N-Acetylgalactosaminyltransferase

Cited by 195 publications

References 41 publications

N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

N-acetylgalactosaminyl transferase-3 is a potential new marker for non-small cell lung cancers

N-Acetylgalactosaminyltransferase-14 as a potential biomarker for breast cancer by immunohistochemistry

A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility

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