Recent advances on glycosyltransferases involved in the biosynthesis of the proteoglycan linkage region

Gao, Jia; Huang, Xuefei

doi:10.1016/bs.accb.2021.10.003

Cited by 3 publications

(1 citation statement)

References 76 publications

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“…At the Golgi, the core protein is glycosylated to first form the GAG-CP linker tetrasaccharide. This requires the expression of several genes coding for different enzymes including glycosyltransferases ( XYLT1, XYLT2, B4GALT7, B3GALT6, B3GAT3 ) 4,5 , kinases ( FAM20B ) 6 , phosphatases ( PXYLP1 ) 7 , and nucleosidases ( CANT1 ) 8 , as well as nucleoside transporters ( SCL26A2, SLC35A2 , and SLC35A3 ) 9 and ion transporters ( SLC10A7 ) 10 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

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Proteoglycans are complex macromolecules formed of glycosaminoglycan chains covalently linked to core proteins through a linker tetrasaccharide common to heparan sulfate proteoglycans (HSPG) and chondroitin sulfate proteoglycans (CSPG). Biosynthesis of a single proteoglycan requires the expression of dozens of genes, which together create the large structural and functional diversity reflected by the numerous diseases or syndromes associated to their genetic variability. Among proteoglycans, HSPG are the most structurally and functionally complex. To decrease this complexity, we retrieved and linked information on pathogenic variants, polymorphism, expression, and literature databases for 50 genes involved in the biosynthesis of HSPG core proteins, heparan sulfate (HS) chains, and their linker tetrasaccharide. This resulted in a new gene organization and biosynthetic pathway representation in which the phenotypic continuum of disorders as linkeropathies and other pathologies could be predictable. Moreover, ubiquitous NDST1, GLCE, HS2ST1, and HS6ST1 appeared to generate ubiquitous heparan sulfate (HS) sequences essential for normal development and homeostasis, whereas the tissue restricted NDST2-4, HS6ST2-3, and HS3ST1-6 appeared to generate specialized HS sequences mainly involved in responsiveness to stimuli. Supported by data on genetic polymorphism and clinical variants, we afford a new vision of HSPG involvement in homeostasis, disease, vulnerability to disease, and behavioral disorders.

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Section: Introductionmentioning

confidence: 99%

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

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Introducing Ion Mobility Mass Spectrometry in Brain Glycosaminoglycomics: Application to Chondroitin/Dermatan Sulfate Octasaccharide Domains

Sarbu,

Seidler,

Clemmer

et al. 2024

J. Am. Soc. Mass Spectrom.

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Glycosaminoglycans (GAGs) are sulfated linear Oglycan chains abundantly expressed in the extracellular matrix (ECM). Among GAGs, chondroitin sulfate (CS) and dermatan sulfate (DS) play important roles at the brain level, where the distribution and location of the sulfates within the CS/DS chains are responsible for numerous biological events. The diversity of the neural hybrid CS/DS expressed in the brain and the need to elucidate their structure gave rise to considerable efforts toward the development of analytical methods able to discover novel regularly and irregularly sulfated domains. In this context, we report here the introduction of ion mobility separation (IMS) mass spectrometry (MS) in brain glycosaminoglycomics. Based on IMS MS and tandem MS (MS/ MS) by collision-induced dissociation (CID), we have developed a powerful approach for the screening and structural analysis of neural CS/DS and optimized and validated the method for the structural analysis of octasaccharides that were released from brain proteoglycans by β-elimination and pooled after chain depolymerization using chondroitin AC lyase. The IMS MS data revealed the separation of CS/DS octamers into mobility families based on the amount of sulfation. Among the discovered oversulfated domains, of major biological importance is the pentasulfated-[4,5-Δ-GlcAGalNAc(IdoAGalNAc) 3 ], for which the (−) nanoESI IMS CID MS/MS analysis disclosed through the presence of distinct drift times, the incidence of two isomers. Moreover, the generated fragment ions revealed an uncommon trisulfated motif and an uncommon pentasulfated motif. Hence, using IMS MS and CID MS/ MS, novel brain-related CS/DS domains of atypical sulfation patterns were discovered and structurally characterized in detail.

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Challenges of targeting tumor microenvironment in prostate cancer

Li,

Chen

2024

New Updates in Tumor Microenvironment [Working Title]

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Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in American men. PCa patients often die of the aggressive forms of the malignancy at advanced stages such as distant metastasis. There are urgent need to understand the molecular mechanisms driving PCa progression and subsequently develop efficient therapeutics to improve men’s health in the US as well as the world. Tumor microenvironment (TME) has been realized to play a critical role in PCa progression and metastasis, and targeting key factors of the TME has become the logical strategy for efficiently controlling PCa malignancy. Stromal cells in prostate tumors secrete growth factors, cytokines, and extracellular matrix (ECM) proteins that provide the TME to fuel cell proliferation, invasion, and metastasis. This review will focus on several key factors influencing TME, which include cancer-associated fibroblasts (CAFs), ECM remodeling, androgen receptor (AR) signaling, inflammation, and hypoxia. We will explain and analyze the biological roles of these factors and their important contributions to PCa malignancy, targeted therapeutics, and drug resistance. Furthermore, we will discuss the contributions of the dysregulation of epigenetic regulators to the complexity of the TME in PCa.

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Recent advances on glycosyltransferases involved in the biosynthesis of the proteoglycan linkage region

Cited by 3 publications

References 76 publications

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Introducing Ion Mobility Mass Spectrometry in Brain Glycosaminoglycomics: Application to Chondroitin/Dermatan Sulfate Octasaccharide Domains

Challenges of targeting tumor microenvironment in prostate cancer

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