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[PMID]:29374258
[Au] Autor:Hirata T; Mishra SK; Nakamura S; Saito K; Motooka D; Takada Y; Kanzawa N; Murakami Y; Maeda Y; Fujita M; Yamaguchi Y; Kinoshita T
[Ad] Endereço:Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, 565-0871, Japan.
[Ti] Título:Identification of a Golgi GPI-N-acetylgalactosamine transferase with tandem transmembrane regions in the catalytic domain.
[So] Source:Nat Commun;9(1):405, 2018 01 26.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Many eukaryotic proteins are anchored to the cell surface via the glycolipid glycosylphosphatidylinositol (GPI). Mammalian GPIs have a conserved core but exhibit diverse N-acetylgalactosamine (GalNAc) modifications, which are added via a yet unresolved process. Here we identify the Golgi-resident GPI-GalNAc transferase PGAP4 and show by mass spectrometry that PGAP4 knockout cells lose GPI-GalNAc structures. Furthermore, we demonstrate that PGAP4, in contrast to known Golgi glycosyltransferases, is not a single-pass membrane protein but contains three transmembrane domains, including a tandem transmembrane domain insertion into its glycosyltransferase-A fold as indicated by comparative modeling. Mutational analysis reveals a catalytic site, a DXD-like motif for UDP-GalNAc donor binding, and several residues potentially involved in acceptor binding. We suggest that a juxtamembrane region of PGAP4 accommodates various GPI-anchored proteins, presenting their acceptor residue toward the catalytic center. In summary, we present insights into the structure of PGAP4 and elucidate the initial step of GPI-GalNAc biosynthesis.
[Mh] Termos MeSH primário: Acetilgalactosamina/química
Glicosilfosfatidilinositóis/química
Complexo de Golgi/metabolismo
N-Acetilgalactosaminiltransferases/química
[Mh] Termos MeSH secundário: Acetilgalactosamina/biossíntese
Motivos de Aminoácidos
Animais
Células CHO
Domínio Catalítico
Cricetulus
Cristalografia por Raios X
Expressão Gênica
Vetores Genéticos/química
Vetores Genéticos/metabolismo
Glicosilfosfatidilinositóis/metabolismo
Complexo de Golgi/ultraestrutura
Seres Humanos
Camundongos
Camundongos Knockout
Modelos Moleculares
Mutação
N-Acetilgalactosaminiltransferases/genética
N-Acetilgalactosaminiltransferases/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Homologia Estrutural de Proteína
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Glycosylphosphatidylinositols); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase); KM15WK8O5T (Acetylgalactosamine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180128
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02799-0


  2 / 1102 MEDLINE  
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[PMID]:29369181
[Au] Autor:Shang H; Sun L; Braun T; Si Q; Tong J
[Ad] Endereço:Department of Obstetrics and Gynecology, Hangzhou First People's Hospital, Nanjing Medical University, Hangzhou, Zhejiang Province, China.
[Ti] Título:Revealing the action mechanisms of dexamethasone on the birth weight of infant using RNA-sequencing data of trophoblast cells.
[So] Source:Medicine (Baltimore);97(4):e9653, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Dexamethasone (DEX) could induce low birth weight of infant, and low birth weight has close associations with glucocorticoid levels, insulin resistance, hypertension, and metabolic syndrome in adulthood. This study was designed to reveal the action mechanisms of DEX on the birth weight of infant.Using quantitative real-time polymerase chain reaction (qRT-PCR), trophoblast cells of human placenta were identified and the optimum treatment time of DEX were determined. Trophoblast cells were treated by DEX (DEX group) or ethanol (control group) (each group had 3 samples), and then were performed with RNA-sequencing. Afterward, the differentially expressed genes (DEGs) were identified by R package, and their potential functions were successively enriched using DAVID database and Enrichr method. Followed by protein-protein interaction (PPI) network was constructed using Cytoscape software. Using Enrichr method and TargetScan software, the transcription factors (TFs) and micorRNAs (miRNAs) targeted the DEGs separately were predicted. Based on MsigDB database, gene set enrichment analysis (GSEA) was performed.There were 391 DEGs screened from the DEX group. Upregulated SRR and potassium voltage-gated channel subfamily J member 4 (KCNJ4) and downregulated GALNT1 separately were enriched in PDZ (an acronym of PSD-95, Dlg, and ZO-1) domain binding and Mucin type O-glycan biosynthesis. In the PPI network, CDK2 and CDK4 had higher degrees. TFs ATF2 and E2F4 and miRNA miR-16 were predicted for the DEGs. Moreover, qRT-PCR analysis confirmed that SRR and KCNJ4 were significantly upregulated.These genes might affect the roles of DEX in the birth weight of infant, and might be promising therapeutic targets for reducing the side effects of DEX.
[Mh] Termos MeSH primário: Peso ao Nascer/genética
Dexametasona/efeitos adversos
Glucocorticoides/efeitos adversos
Análise de Sequência de RNA
Trofoblastos/efeitos dos fármacos
[Mh] Termos MeSH secundário: Fator 2 Ativador da Transcrição/efeitos dos fármacos
Peso ao Nascer/efeitos dos fármacos
Quinase 2 Dependente de Ciclina/efeitos dos fármacos
Quinase 4 Dependente de Ciclina/efeitos dos fármacos
Fator de Transcrição E2F4/efeitos dos fármacos
Feminino
Seres Humanos
Recém-Nascido
MicroRNAs/efeitos dos fármacos
N-Acetilgalactosaminiltransferases/efeitos dos fármacos
Placenta/citologia
Canais de Potássio Corretores do Fluxo de Internalização/efeitos dos fármacos
Gravidez
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ATF2 protein, human); 0 (Activating Transcription Factor 2); 0 (E2F4 Transcription Factor); 0 (E2F4 protein, human); 0 (Glucocorticoids); 0 (KCNJ4 protein, human); 0 (MIRN16 microRNA, human); 0 (MicroRNAs); 0 (Potassium Channels, Inwardly Rectifying); 7S5I7G3JQL (Dexamethasone); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase); EC 2.7.11.22 (CDK2 protein, human); EC 2.7.11.22 (CDK4 protein, human); EC 2.7.11.22 (Cyclin-Dependent Kinase 2); EC 2.7.11.22 (Cyclin-Dependent Kinase 4)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009653


  3 / 1102 MEDLINE  
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[PMID]:29287114
[Au] Autor:Shimbo M; Suzuki R; Fuseya S; Sato T; Kiyohara K; Hagiwara K; Okada R; Wakui H; Tsunakawa Y; Watanabe H; Kimata K; Narimatsu H; Kudo T; Takahashi S
[Ad] Endereço:Department of Anatomy and Embryology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
[Ti] Título:Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2.
[So] Source:PLoS One;12(12):e0190333, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chondroitin sulfate (CS) is a sulfated glycosaminoglycan (GAG) chain. In cartilage, CS plays important roles as the main component of the extracellular matrix (ECM), existing as side chains of the major cartilage proteoglycan, aggrecan. Six glycosyltransferases are known to coordinately synthesize the backbone structure of CS; however, their in vivo synthetic mechanism remains unknown. Previous studies have suggested that two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. Indeed, t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in CS content in cartilage compared with wild-type (WT) mice. To reveal the synergetic roles of t1 and t2 in CS synthesis in vivo, we generated systemic single and double knockout (DKO) mice and cartilage-specific t1 and t2 double knockout (Col2-DKO) mice. DKO mice exhibited postnatal lethality, whereas t2 KO mice showed normal size and skeletal development. Col2-DKO mice survived to adulthood and showed severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice revealed disrupted endochondral ossification, characterized by drastic GAG reduction in the ECM. Moreover, DKO cartilage had reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with WT cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage had the same proliferation rate as WT chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves had an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage showed that the expression levels of Col2a1 and Ptch1 transcripts tended to decrease in DKO compared with those in WT mice. The CS content in DKO cartilage was decreased compared with that in t1 KO cartilage but was not completely absent. These results suggest that aberrant ECM caused by CS reduction disrupted endochondral ossification. Overall, we propose that both t1 and t2 are necessary for CS synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage.
[Mh] Termos MeSH primário: Genes Letais
N-Acetilgalactosaminiltransferases/genética
Osteocondrodisplasias/genética
[Mh] Termos MeSH secundário: Animais
Apoptose/genética
Proliferação Celular/genética
Células Cultivadas
Condrócitos/patologia
Camundongos
Camundongos Knockout
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Messenger); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.- (chondroitin sulfate N-acetylgalactosaminyltransferase-1); EC 2.4.1.- (chondroitin sulfate N-acetylgalactosaminyltransferase-2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180207
[Lr] Data última revisão:
180207
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171230
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190333


  4 / 1102 MEDLINE  
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[PMID]:29227978
[Au] Autor:Wu J; Chen X; Bao Q; Duan R; Jin Y; Shui Y; Yao B; Lu X; Wang Y; Cui H; Li L; Yuan H; Ma C
[Ad] Endereço:Department of Developmental Genetics, Nanjing Medical University, Nanjing, China.
[Ti] Título:Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14.
[So] Source:Cell Physiol Biochem;44(3):998-1010, 2017.
[Is] ISSN:1421-9778
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIMS: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. METHODS: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. RESULTS: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. CONCLUSION: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/patologia
N-Acetilgalactosaminiltransferases/metabolismo
Fator de Transcrição Sp7/metabolismo
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/uso terapêutico
Antineoplásicos/toxicidade
Apoptose/efeitos dos fármacos
Neoplasias da Mama/tratamento farmacológico
Neoplasias da Mama/mortalidade
Linhagem Celular Tumoral
Intervalo Livre de Doença
Feminino
Seres Humanos
Imuno-Histoquímica
Camundongos
Camundongos Nus
N-Acetilgalactosaminiltransferases/antagonistas & inibidores
N-Acetilgalactosaminiltransferases/genética
Proteínas Proto-Oncogênicas c-bcl-2/metabolismo
Interferência de RNA
RNA Interferente Pequeno/metabolismo
Fator de Transcrição Sp7/antagonistas & inibidores
Fator de Transcrição Sp7/genética
Taxa de Sobrevida
Transplante Heterólogo
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Proto-Oncogene Proteins c-bcl-2); 0 (RNA, Small Interfering); 0 (Sp7 Transcription Factor); 0 (bcl-2-Associated X Protein); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (UDP-N-acetyl-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 14, human)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180118
[Lr] Data última revisão:
180118
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1159/000485400


  5 / 1102 MEDLINE  
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[PMID]:29061174
[Au] Autor:Al Dhaibani MA; Allingham-Hawkins D; El-Hattab AW
[Ad] Endereço:Pediatrics Department, Tawam Hospital, Al-Ain, United Arab Emirates.
[Ti] Título:De novo chromosome 7q36.1q36.2 triplication in a child with developmental delay, growth failure, distinctive facial features, and multiple congenital anomalies: a case report.
[So] Source:BMC Med Genet;18(1):118, 2017 Oct 23.
[Is] ISSN:1471-2350
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Studying human genome using chromosomal microarrays has significantly improved the accuracy and yield of diagnosing genomic disorders. Chromosome 7q36 deletions and duplications are rare genomic disorders that have been reported in a limited number of children with developmental delay, growth retardation, and congenital malformation. Altered dosage of SHH and HLXB9, both located in 7q36.3, is believed to play roles in the phenotypes associated with these rearrangements. In this report we describe a child with 7q36.1q36.2 triplication that is proximal to the 7q36.3 region. In addition to the clinical description, we discuss the genes located in the triplicated region. CASE PRESENTATION: We report a 22 month old male child with a de novo 1.35 Mb triplication at 7q36.1q36.2. His prenatal course was complicated by oligohydramnios, intrauterine growth restriction, and decreased fetal movement. Hypotonia, respiratory distress, and feeding difficulty were observed in the neonatal period. He also had developmental delay, cardiovascular malformation, growth failure with microcephaly, short stature, and underweight, sensorineural hearing loss, myopia, astigmatism, cryptorchidism, hypospadias, microphallus, lower extremity length discrepancy, bifid uvula, single palmer creases, and distinctive facial features including straight eyebrows, ptosis, up-slanted palpebral fissures, broad nasal bridge, low-set and posteriorly rotated ears, small mouth with thick lower lip, microretrognathia, and high-arched palate. CONCLUSIONS: The child presented here had developmental delay, distinctive facial features, multiple congenital anomalies, and 7q36.1q36.2 triplication. This triplication, which was found to be de novo, has not been previously described and is believed to result in the observed phenotype. The triplicated region harbors the GALNTL5, GALNT11, KMT2C, XRCC2, and ACTR3B genes. GALNT11 encodes a membrane-bound polypeptide N-acetylgalactosaminyltransferase that can O-glycosylate NOTCH1 leading to the activation of the Notch signaling pathway. Therefore, increased GALNT11 dosage can potentially alter the Notch signaling pathway explaining the pathogenicity of 7q36 triplication. Studying further cases with similar genomic rearrangements is needed to make final conclusions about the pathogenicity of this triplication.
[Mh] Termos MeSH primário: Anormalidades Múltiplas/genética
Duplicação Cromossômica
Cromossomos Humanos Par 7/genética
[Mh] Termos MeSH secundário: Amplificação de Genes
Seres Humanos
Lactente
Masculino
N-Acetilgalactosaminiltransferases/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.4.1.- (GALNT11 protein, human); EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171027
[Lr] Data última revisão:
171027
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171025
[St] Status:MEDLINE
[do] DOI:10.1186/s12881-017-0482-8


  6 / 1102 MEDLINE  
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[PMID]:28817611
[Au] Autor:Veyhl J; Dunn RJ; Johnston WL; Bennett A; Zhang LW; Dennis JW; Schachter H; Culotti JG
[Ad] Endereço:Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
[Ti] Título:The directed migration of gonadal distal tip cells in Caenorhabditis elegans requires NGAT-1, a ß1,4-N-acetylgalactosaminyltransferase enzyme.
[So] Source:PLoS One;12(8):e0183049, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Glycoproteins such as growth factor receptors and extracellular matrix have well-known functions in development and cancer progression, however, the glycans at sites of modification are often heterogeneous molecular populations which makes their functional characterization challenging. Here we provide evidence for a specific, discrete, well-defined glycan modification and regulation of a stage-specific cell migration in Caenorhabditis elegans. We show that a chain-terminating, putative null mutation in the gene encoding a predicted ß1,4-N-acetylgalactosaminyltransferase, named ngat-1, causes a maternally rescued temperature sensitive (ts) defect in the second phase of the three phase migration pattern of the posterior, but not the anterior, hermaphrodite Distal Tip Cell (DTC). An amino-terminal partial deletion of ngat-1 causes a similar but lower penetrance ts phenotype. The existence of multiple ts alleles with distinctly different molecular DNA lesions, neither of which is likely to encode a ts protein, indicates that NGAT-1 normally prevents innate temperature sensitivity for phase 2 DTC pathfinding. Temperature shift analyses indicate that the ts period for the ngat-1 mutant defect ends by the beginning of post-embryonic development-nearly 3 full larval stages prior to the defective phase 2 migration affected by ngat-1 mutations. NGAT-1 homologs generate glycan-terminal GalNAc-ß1-4GlcNAc, referred to as LacdiNAc modifications, on glycoproteins and glycolipids. We also found that the absence of the GnT1/Mgat1 activity [UDP-N-acetyl-D-glucosamine:α-3-D-mannoside ß-1,2-N-acetylglucosaminyltransferase 1 (encoded by C. elegans gly-12, gly-13, and gly-14 and homologous to vertebrate GnT1/Mgat1)], causes a similar spectrum of DTC phenotypes as ngat-1 mutations-primarily affecting posterior DTC phase 2 migration and preventing manifestation of the same innate ts period as ngat-1. GnT1/Mgat1 is a medial Golgi enzyme known to modify mannose residues and initiate N-glycan branching, an essential step in the biosynthesis of hybrid, paucimannose and complex-type N-glycans. Quadruple mutant animals bearing putative null mutations in ngat-1 and the three GnT genes (gly-12, gly-13, gly-14) were not enhanced for DTC migration defects, suggesting NGAT-1 and GnT1 act in the same pathway. These findings suggest that GnTI generates an N-glycan substrate for NGAT-1 modification, which is required at restrictive temperature (25°C) to prevent, stabilize, reverse or compensate a perinatal thermo-labile process (or structure) causing late larval stage DTC phase 2 migration errors.
[Mh] Termos MeSH primário: Proteínas de Caenorhabditis elegans/metabolismo
Caenorhabditis elegans/metabolismo
Movimento Celular
Gônadas/citologia
N-Acetilgalactosaminiltransferases/genética
N-Acetilglucosaminiltransferases/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Animais
Caenorhabditis elegans/citologia
Caenorhabditis elegans/genética
Proteínas de Caenorhabditis elegans/genética
Gônadas/embriologia
Gônadas/metabolismo
Mutação
N-Acetilgalactosaminiltransferases/metabolismo
N-Acetilglucosaminiltransferases/genética
Neurônios/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caenorhabditis elegans Proteins); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.- (N-Acetylglucosaminyltransferases); EC 2.4.1.- (NGAT-1 protein, C elegans)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183049


  7 / 1102 MEDLINE  
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[PMID]:28719662
[Au] Autor:Herbomel GG; Rojas RE; Tran DT; Ajinkya M; Beck L; Tabak LA
[Ad] Endereço:Section on Biological Chemistry, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, United States of America.
[Ti] Título:The GalNAc-T Activation Pathway (GALA) is not a general mechanism for regulating mucin-type O-glycosylation.
[So] Source:PLoS One;12(7):e0179241, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mucin-type O-glycosylation is initiated by the UDP-GalNAc polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes. Their activity results in the GalNAc α1-O-Thr/Ser structure, termed the Tn antigen, which is further decorated with additional sugars. In neoplastic cells, the Tn antigen is often overexpressed. Because O-glycosylation is controlled by the activity of GalNAc-Ts, their regulation is of great interest. Previous reports suggest that growth factors, EGF or PDGF, induce Golgi complex-to-endoplasmic reticulum (ER) relocation of both GalNAc-Ts and Tn antigen in HeLa cells, offering a mechanism for Tn antigen overexpression termed "GALA". However, we were unable to reproduce these findings. Upon treatment of HeLa cells with either EGF or PDGF we observed no change in the co-localization of endogenous GalNAc-T1, GalNAc-T2 or Tn antigen with the Golgi complex marker TGN46. There was also no enhancement of localization with the ER marker calnexin. We conclude that growth factors do not cause redistribution of GalNAc-Ts from the Golgi complex to the ER in HeLa cells.
[Mh] Termos MeSH primário: Mucinas/metabolismo
N-Acetilgalactosaminiltransferases/metabolismo
[Mh] Termos MeSH secundário: Antígenos Glicosídicos Associados a Tumores/metabolismo
Retículo Endoplasmático/efeitos dos fármacos
Retículo Endoplasmático/metabolismo
Ativação Enzimática/efeitos dos fármacos
Fator de Crescimento Epidérmico/farmacologia
Glicosilação/efeitos dos fármacos
Complexo de Golgi/efeitos dos fármacos
Complexo de Golgi/metabolismo
Células HeLa
Seres Humanos
Mucinas/química
Fator de Crescimento Derivado de Plaquetas/farmacologia
Transporte Proteico/efeitos dos fármacos
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Tumor-Associated, Carbohydrate); 0 (Mucins); 0 (Platelet-Derived Growth Factor); 0 (Tn antigen); 62229-50-9 (Epidermal Growth Factor); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170927
[Lr] Data última revisão:
170927
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179241


  8 / 1102 MEDLINE  
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[PMID]:28719645
[Au] Autor:Bard F; Chia J
[Ad] Endereço:Institute of Molecular and Cell Biology, Proteos, Singapore, Singapore, and Department of Biochemistry, National University of Singapore, Singapore, Singapore.
[Ti] Título:Comment on "The GalNAc-T Activation Pathway (GALA) is not a general mechanism for regulating mucin-type O-glycosylation".
[So] Source:PLoS One;12(7):e0180005, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Mucinas
N-Acetilgalactosaminiltransferases
[Mh] Termos MeSH secundário: Glicopeptídeos
Glicosilação
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Glycopeptides); 0 (Mucins); EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171106
[Lr] Data última revisão:
171106
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180005


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[PMID]:28698248
[Au] Autor:Chumpen Ramirez S; Ruggiero FM; Daniotti JL; Valdez Taubas J
[Ad] Endereço:Centro de Investigaciones en Química Biológica de Córdoba (CIQUIBIC), CONICET, Universidad Nacional de Córdoba, Córdoba, Argentina jvaldezt@dqb.fcq.unc.edu.ar.
[Ti] Título:Ganglioside glycosyltransferases are S-acylated at conserved cysteine residues involved in homodimerisation.
[So] Source:Biochem J;474(16):2803-2816, 2017 Aug 07.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Ganglioside glycosyltransferases (GGTs) are type II membrane proteins bearing a short N-terminal cytoplasmic tail, a transmembrane domain (TMD), and a lumenal catalytic domain. The expression and activity of these enzymes largely determine the quality of the glycolipids that decorate mammalian cell membranes. Many glycosyltransferases (GTs) are themselves glycosylated, and this is important for their proper localisation, but few if any other post-translational modifications of these proteins have been reported. Here, we show that the GGTs, ST3Gal-V, ST8Sia-I, and ß4GalNAcT-I are S-acylated at conserved cysteine residues located close to the cytoplasmic border of their TMDs. ST3Gal-II, a GT that sialylates glycolipids and glycoproteins, is also S-acylated at a conserved cysteine located in the N-terminal cytoplasmic tail. Many other GTs also possess cysteine residues in their cytoplasmic regions, suggesting that this modification occurs also on these GTs. S-acylation, commonly known as palmitoylation, is catalysed by a family of palmitoyltransferases (PATs) that are mostly localised at the Golgi complex but also at the endoplasmic reticulum (ER) and the plasma membrane. Using GT ER retention mutants, we found that S-acylation of ß4GalNAcT-I and ST3Gal-II takes place at different compartments, suggesting that these enzymes are not substrates of the same PAT. Finally, we found that cysteines that are the target of S-acylation on ß4GalNAcT-I and ST3Gal-II are involved in the formation of homodimers through disulphide bonds. We observed an increase in ST3Gal-II dimers in the presence of the PAT inhibitor 2-bromopalmitate, suggesting that GT homodimerisation may be regulating S-acylation.
[Mh] Termos MeSH primário: N-Acetilgalactosaminiltransferases/metabolismo
Processamento de Proteína Pós-Traducional
Sialiltransferases/metabolismo
[Mh] Termos MeSH secundário: Acilação
Sequência de Aminoácidos
Animais
Células CHO
Linhagem Celular
Sequência Conservada
Cricetulus
Cisteína/metabolismo
Dimerização
Seres Humanos
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Microscopia de Fluorescência
Mutação
N-Acetilgalactosaminiltransferases/química
N-Acetilgalactosaminiltransferases/genética
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/metabolismo
Filogenia
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes de Fusão/química
Proteínas Recombinantes de Fusão/metabolismo
Sialiltransferases/química
Sialiltransferases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Luminescent Proteins); 0 (Peptide Fragments); 0 (Recombinant Fusion Proteins); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.165 (beta-1,4-N-acetyl-galactosaminyl transferase 1, human); EC 2.4.99.- (Sialyltransferases); EC 2.4.99.4 (beta-galactoside alpha-2,3-sialyltransferase); EC 2.4.99.8 (alpha-N-acetylneuraminate alpha-2,8-sialyltransferase); EC 2.4.99.9 (haematoside synthetase); K848JZ4886 (Cysteine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170713
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170124


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[PMID]:28672761
[Au] Autor:Lorenz V; Cejas RB; Bennett EP; Nores GA; Irazoqui FJ
[Ad] Endereço:, and.
[Ti] Título:Functional control of polypeptide GalNAc-transferase 3 through an acetylation site in the C-terminal lectin domain.
[So] Source:Biol Chem;398(11):1237-1246, 2017 Oct 26.
[Is] ISSN:1437-4315
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:O-GalNAc glycans are important structures in cellular homeostasis. Their biosynthesis is initiated by members of the polypeptide GalNAc-transferase (ppGalNAc-T) enzyme family. Mutations in ppGalNAc-T3 isoform cause diseases (congenital disorders of glycosylation) in humans. The K626 residue located in the C-terminal ß-trefoil fold of ppGalNAc-T3 was predicted to be a site with high likelihood of acetylation by CBP/p300 acetyltransferase. We used a site-directed mutagenesis approach to evaluate the role of this acetylation site in biological properties of the enzyme. Two K626 mutants of ppGalNAc-T3 (T3K626Q and T3K626A) had GalNAc-T activities lower than that of wild-type enzyme. Direct and competitive interaction assays revealed that GalNAc recognition by the lectin domain was altered in the mutants. The presence of GlcNAc glycosides affected the interaction of the three enzymes with mucin-derived peptides. In GalNAc-T activity assays, the presence of GlcNAc glycosides significantly inhibited activity of the mutant (T3K626Q) that mimicked acetylation. Our findings, taken together, reveal the crucial role of the K626 residue in the C-terminal ß-trefoil fold in biological properties of human ppGalNAc-T3. We propose that acetylated residues on ppGalNAc-T3 function as control points for enzyme activity, and high level of GlcNAc glycosides promote a synergistic regulatory mechanism, leading to a metabolically disordered state.
[Mh] Termos MeSH primário: Lectinas/química
Lectinas/metabolismo
N-Acetilgalactosaminiltransferases/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Seres Humanos
N-Acetilgalactosaminiltransferases/genética
N-Acetilgalactosaminiltransferases/isolamento & purificação
Mutação Puntual
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lectins); EC 2.4.1.- (N-Acetylgalactosaminyltransferases); EC 2.4.1.41 (polypeptide N-acetylgalactosaminyltransferase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170705
[St] Status:MEDLINE



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