| 2010 |
CHSY1 is a secreted FRINGE enzyme required for chondroitin sulfate biosynthesis and for modulation of NOTCH signaling; loss of CHSY1 triggers massive production of JAG1 and subsequent NOTCH activation, which is reversed by wild-type but not catalytically dead CHSY1, demonstrating that its Fringe enzymatic activity is required for NOTCH regulation. |
Patient fibroblast secretion assay, RNAi knockdown in osteoblasts and glioblastoma cells, rescue with wild-type vs. catalytic-dead CHSY1 construct, zebrafish chsy1 morpholino knockdown |
American journal of human genetics |
High |
21129727
|
| 2012 |
Chsy1 is required for joint patterning and bone density in mice; Chsy1 knockout causes chondrodysplasia, decreased bone density, and ectopic joint formation in distal digits associated with a shift in cell orientation and imbalance in chondroitin sulfation. |
Chsy1 knockout mouse model; skeletal phenotype analysis, chondroitin sulfation assessment |
Developmental biology |
High |
22280990
|
| 2013 |
CHSY1 has two glycosyltransferase activities (GlcUA transferase and GalNAc transferase) responsible for adding disaccharide units to chondroitin sulfate chains; the F362S missense mutation reduces both activities by ~50% and abrogates the cooperative elongation of chains initiated by chondroitin N-acetylgalactosaminyltransferase-1 (CSGALNACT1), demonstrating that CHSY1 regulates chain number/length cooperatively with CSGALNACT1. |
Recombinant wild-type and F362S mutant enzyme expression, in vitro glycosyltransferase activity assay, cell-based complementation |
Biochimica et biophysica acta |
High |
23811343
|
| 2015 |
TGF-β induces CHSY1 expression in nucleus pulposus cells via MAPK signaling and activation of transcription factors c-Jun and Sp1; knockdown of c-Jun or Sp1 reduces TGF-β-mediated CHSY1 promoter activity and sulfated GAG accumulation; silencing CHSY1 reduces TGF-β-induced sulfated GAG accumulation. |
Real-time PCR, Western blot, lentiviral knockdown, CHSY1 promoter reporter assay in nucleus pulposus cells |
Cellular physiology and biochemistry |
Medium |
26356269
|
| 2017 |
CHSY1 promotes hepatocellular carcinoma cell migration, invasion, and EMT by increasing cell-surface chondroitin sulfate that facilitates sonic hedgehog binding and Hedgehog pathway signaling; pharmacological Hedgehog inhibition reverses CHSY1-induced migration, invasion, and lung metastasis. |
CHSY1 overexpression and silencing in HCC cell lines, Hedgehog pathway inhibitor (vismodegib), in vivo lung metastasis assay |
Cancer letters |
Medium |
28652022
|
| 2018 |
TGF-β1-mediated upregulation of CHSY1 mRNA in vascular smooth muscle cells occurs via a ROS/NADPH oxidase (Nox)-dependent pathway involving Smad2 linker region phosphorylation and MAPK activation; Nox inhibitors (DPI, apocynin) block both Smad2 linker phosphorylation and CHSY1 mRNA induction. |
Western blotting for signaling intermediates, qRT-PCR for gene expression, pharmacological inhibition of Nox, fluorescence-based ROS measurement in VSMCs |
Journal of cell communication and signaling |
Medium |
30417274
|
| 2018 |
Polyamines stimulate CHSY1 protein synthesis by destabilizing an RNA G-quadruplex (G4) structure in the 5'-UTR of CHSY1 mRNA (positions -202 to -117 relative to initiation codon); site-directed mutagenesis that prevents G4 formation abolishes the polyamine-stimulated increase in CHSY1 synthesis. |
Polyamine depletion/supplementation, CHSY1 protein quantification, NMR/structural analysis of 5'-UTR G4, site-directed mutagenesis of G4 sequences |
The Biochemical journal |
High |
30401686
|
| 2019 |
Endothelin-1 increases CHSY-1 protein levels in bovine aortic endothelial cells via ETB receptor signaling through Rho kinase and actin cytoskeletal rearrangement, leading to TGF-β type I receptor transactivation and Smad2C phosphorylation; this pathway does not involve MMPs. |
Western blotting with pharmacological inhibitors (BQ788, Y27632, cytochalasin D, GM6001) in BAECs |
The Journal of pharmacy and pharmacology |
Medium |
30809816
|
| 2021 |
ET-1 increases CHSY1 expression in human VSMCs through transactivation of both EGF receptor and TGF-β receptor; EGF receptor transactivation by ET-1 is dependent on NADPH oxidase (NOX) and ERK1/2 phosphorylation. |
Western blot with pharmacological inhibitors (bosentan, AG1478, DPI, SB431542) in human VSMCs |
Cell journal |
Medium |
34837677
|
| 2022 |
CGRP from sensory nerves maintains intervertebral disc chondroitin sulfate homeostasis by regulating nucleus pulposus cell CHSY1 expression via the CGRP receptor component RAMP1 and CREB signaling; CHSY1 knockout mice phenocopy sensory denervation-induced ECM disorder, placing CHSY1 downstream of the CGRP/RAMP1/CREB axis. |
Genetic sensory denervation, CGRP knockdown mouse model, CHSY1 knockout mice, in vitro CGRP treatment with RAMP1/CREB pathway analysis |
Advanced science |
High |
36047655
|
| 2022 |
Chsy1 deficiency in chondrocytes reduces extracellular matrix production and promotes endochondral osteogenesis by upregulating BMP signaling; BMP inhibitor LDN193189 rescues the ECM and osteogenesis defects caused by Chsy1 knockdown, placing Chsy1 as a negative regulator of BMP signaling in cartilage. |
Lentiviral Chsy1 knockdown in ATDC5 chondrocytes, BMP inhibitor rescue, gene expression analysis (Col2a1, Sox9, Col10a1, Runx2, Mmp13, Mmp3), primary OA rat chondrocyte experiments |
Gene |
Medium |
35390446
|
| 2023 |
Chsy1 knockdown at peripheral nerve lesion sites decreases versican core protein accumulation in perineurium, associated with functional recovery of compound muscle action potential after end-to-side neurorrhaphy, indicating that CHSY1-synthesized chondroitin sulfate chains stabilize versican in the extracellular matrix. |
In vivo siRNA transfection in rat neurorrhaphy model, confocal microscopy, Western blotting, electrophysiology (compound muscle action potential) |
Molecules |
Medium |
37175152
|
| 2023 |
CHSY1 promotes CD8+ T cell exhaustion and PD-L1 upregulation through activation of the succinate metabolism pathway and the PI3K/AKT/HIF1A pathway, facilitating colorectal cancer liver metastasis; artemisinin inhibits CHSY1 activity and synergizes with anti-PD1. |
CRISPR/Cas9 in vivo mouse screen, in vitro and in vivo CHSY1 KD experiments, metabolomic analysis |
Journal of experimental & clinical cancer research |
Medium |
37749638
|
| 2025 |
CHSY1 forms four heterodimeric complexes (CHSY1-CHPF, CHSY1-CHPF2, CHSY3-CHPF, CHSY3-CHPF2) that polymerize chondroitin sulfate chains; cryo-EM structure and mutational analysis confirm that CHSY1 (and CHSY3) are the catalytically active bifunctional glycosyltransferases, while CHPF and CHPF2 play a stabilizing role; chain polymerization follows a non-processive, disruptive mechanism. |
Cryo-EM structure of CHSY3-CHPF complex, in vitro glycosylation assay with fluorescent substrates, mutational analysis of catalytic sites, in cellulo complementation assay |
bioRxivpreprint |
High |
bio_10.1101_2025.03.21.644485
|
| 2026 |
CANT1 binds and stabilizes β-catenin, which translocates to the nucleus to activate CHSY1 transcription via TCF4; loss of CANT1/β-catenin signaling reduces CHSY1 expression and consequently reduces GAG and proteoglycan (ACAN) and COL2α1 production, causing skeletal ECM defects. |
Protein binding assays (CANT1-β-catenin interaction), nuclear translocation assay, CHSY1 gene activation assays, ECM component quantification in skeletal cells |
Research (Washington, D.C.) |
Medium |
41928906
|