Sulfotransferases in glycosaminoglycan biosynthesis

Kusche-Gullberg, Marion; Kjellén, Lena

doi:10.1016/j.sbi.2003.08.002

Cited by 266 publications

(160 citation statements)

References 64 publications

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“…3 DNA methylation analysis of the 3-OST3A promoter CpG island ( Figure S1A) showed strong hypermethylation in T-47D and MDA-derived cells, while in MCF-7 cells, hypermethylation only occurred downstream from the TSS ( Figure 1B). In contrast, 3-OST3A was not subject to DNA methylation in SKBR3 and MCF-10A cells ( Figure 1B and S1B).…”

Section: --Ost3a Is Differentially Repressed In Breast Cancer Cell Lmentioning

confidence: 99%

“…2 During biosynthesis, HS are subjected to marked structural modifications -mainly epimerization, Ndeacetylation, N-and O-sulfation, catalyzed by numerous enzymes, including HS-Osulfotransferases. 3,4 The range of biological functions of HS ultimately depends on the fine structure of their polysaccharide chain. The 3-O-sulfotransferases (3-OST) form the largest multigene family of HS modifying enzymes with seven different isoforms, catalyzing Osulfation at position 3 of glucosamine (GlcN) residues to produce at least two functionally distinct 3-O-sulfated motifs.…”

Section: Introductionmentioning

confidence: 99%

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The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

et al. 2016

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The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer Mao, X.; Gauche, C.; Coughtrie, M. W. H.; Bui, C.; Gulberti, S.; Merhi-Soussi, F. Citation for published version (APA):Mao, X., Gauche, C., Coughtrie, M. W. H., Bui, C., Gulberti, S., Merhi-Soussi, F., ... Fournel-Gigleux, S. (2016). The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer. Oncogene, 35, 5043-5055. DOI: 10.1038/onc.2016 General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.• Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research.• You may not further distribute the material or use it for any profit-making activity or commercial gain.• You may freely distribute the URL identifying the publication in the public portal. Take down policyIf you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Heparan sulfate (HS) proteoglycan chains are key components of the breast tumor microenvironment that critically influence the behavior of cancer cells. It is established that abnormal synthesis and processing of HS play a prominent role in tumorigenesis albeit mechanisms remain mostly obscure. HS function is mainly controlled by sulfotransferases, and here we report a novel cellular and pathophysiological significance for the 3--O--sulfotransferase 3--OST3A (HS3ST3A), catalyzing the final maturation step of HS, in breast cancer. We show that 3--OST3A is epigenetically repressed in all breast cancer cell lines of a panel representative of distinct molecular subgroups, except in HER2--positive (HER2+) SKBR3 cells. Epigenetic mechanisms involved both DNA methylation and histone modifications, producing different repressive chromatin environments depending on the cell molecular signature. Gain and loss of function experiments by cDNA and siRNA transfection revealed profound effects of 3--OST3A expression on cell behavior including apoptosis, proliferation, response to trastuzumab in vitro and tumor growth in xenografted mice. 3--OST3A exerted dual activities acting as tumor--suppressor in lumA--MCF--7 and triple negative--MDA--MB--231 cells, or as an oncogenic factor in HER2+--SKBR3 cells. Mechanistically, fluorescence--resonance energy transfer (FRET)--fluorescence--lifetime imaging microscopy (FLIM) experiments indicated that the effects of 3--OST3A in MCF--7 cells were mediated by altered interactions between HS and fibroblast growth factor--7 (FGF--7). Further, this interplay between HS and FGF--7 modulated downstream ERK, AKT and p38 cascades, suggesting that altering 3--O--sulfation affects FGFR...

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Section: --Ost3a Is Differentially Repressed In Breast Cancer Cell Lmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

et al. 2016

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“…In L. pneumophila, the dotD mutant strain was shown to be unable to replicate in A. castellanii and in HL-60-derived human macrophages (Yerushalmi et al, 2005). We identified a lipobox-motif in the N-terminus of DotD ("ITGC"), as well as in the DotC ("LIGC") and the IcmN ("MTGC") protein, shown to be necessary for the function of DotC and DotD in L. pneumophila (Yerushalmi et al, 2005 (Mougous et al, 2002) and they are involved in cell-cell interactions, host-pathogen interactions, extracellular traffic or in root modulation by Rhizobia (Hanin et al, 1997;Negishi et al, 2001;Mougous et al, 2002;Kusche-Gullberg et al, 2003;Del Papa et al, 2007).…”

Section: Screening For Virulence Genes Of L Oakridgensis Atcc 33761 mentioning

confidence: 99%

Legionella oakridgensis ATCC 33761 genome sequence and phenotypic characterization reveals its replication capacity in amoebae

Brzuszkiewicz

Schulz

Rydzewski

et al. 2013

International Journal of Medical Microbiology

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Legionella oakridgensis is able to cause Legionnaires` disease, but is less virulent compared to L. pneumophila strains and very rarely associated with human disease. L. oakridgensis is the only species of the family legionellae which is able to grow on media without additional cysteine. In contrast to earlier publications, we found that L. oakridgensis is able to multiply in amoebae. We sequenced the genome of L. oakridgensis type strain OR-10 (ATCC 33761).The genome is smaller than the other yet sequenced Legionella genomes and has a higher G+C-content of 40.9%. L. oakridgensis lacks a flagellum and it also lacks all genes of the flagellar regulon except of the alternative sigma-28 factor FliA and the anti-sigma-28 factor

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“…18 Glycosaminoglycans (GAGs), including chondroitin sulfate (CS), are involved in a wide variety of biological processes. [20][21][22][23] Part of the CS biosynthesis in the Golgi entails the transfer of sulfate groups to specific carbon positions of the disaccharide units by sulfotransferase enzymes. [20][21][22][23] The balance of chondroitin sulfation is tightly controlled through spatial and temporal expression of distinct chondroitin sulfotransferase genes.…”

Section: Introductionmentioning

confidence: 99%

C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome

et al. 2012

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Costello syndrome is a pediatric genetic disorder linked to oncogenic germline mutations in the HRAS gene. The disease is characterized by multiple developmental abnormalities, as well as predisposition to malignancies. Our recent observation that heart tissue from patients with Costello syndrome showed a loss of the glycosaminoglycan chondroitin-4-sulfate (C4S) inspired our present study aimed to explore a functional involvement of the chondroitin sulfate (CS) biosynthesis gene Carbohydrate sulfotransferase 11/Chondroitin-4-sulfotransferase-1 (CHST11/C4ST-1), as well as an impaired chondroitin sulfation balance, as a downstream mediator of oncogenic HRAS in Costello syndrome. Here we demonstrate a loss of C4S, as well as a reduction in C4ST-1 mRNA and protein expression, in primary fibroblasts from Costello syndrome patients. We go on to show that expression of oncogenic HRAS in normal fibroblasts can repress C4ST-1 expression, whereas interference with oncogenic HRAS signaling in Costello syndrome fibroblasts elevated C4ST-1 expression, thus identifying C4ST-1 as a negatively regulated target gene of HRAS signaling. Importantly, we show that forced expression of C4ST-1 in Costello fibroblasts could rescue the proliferation and elastogenesis defects associated with oncogenic HRAS signaling in these cells. Our results indicate reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome. Thus, our work identifies C4ST-1-dependent chondroitin sulfation as a downstream vulnerability in oncogenic RAS signaling, which might be pharmacologically exploited in future treatments of not only Costello syndrome and other RASopathies, but also human cancers associated with activating RAS mutations.

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Sulfotransferases in glycosaminoglycan biosynthesis

Cited by 266 publications

References 64 publications

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

The heparan sulfate sulfotransferase 3-OST3A (HS3ST3A) is a novel tumor regulator and a prognostic marker in breast cancer

Legionella oakridgensis ATCC 33761 genome sequence and phenotypic characterization reveals its replication capacity in amoebae

C4ST-1/CHST11-controlled chondroitin sulfation interferes with oncogenic HRAS signaling in Costello syndrome

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