ArticleThe Journal of biological chemistry2011
Cellular content of UDP-N-acetylhexosamines controls hyaluronan synthase 2 expression and correlates with O-linked N-acetylglucosamine modification of transcription factors YY1 and SP1.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 62 citations in OpenAlex.
- Cross-talk between glycosylation pathways: Mechanistic insights and implications for human diseases.Molecular metabolism · 2026Review
- Sesamol regulates AQP3 and HAS2 via MAPK signaling for skin barrier protection an in vitro and molecular docking study.Scientific reports · 2025Article
- Activated cardiac fibroblasts are a primary source of high-molecular-weight hyaluronan production.American journal of physiology. Cell physiology · 2025Article
- Enzyme variants in biosynthesis and biological assessment of different molecular weight hyaluronan.AMB Express · 2024Article
- Review
- Aggrecan and Hyaluronan: The Infamous Cartilage Polyelectrolytes - Then and Now.Advances in experimental medicine and biology · 2023Article
- Mechanisms of coordinating hyaluronan and glycosaminoglycan production by nucleotide sugars.American journal of physiology. Cell physiology · 2022Review
- The Glycobiology of Pulmonary Arterial Hypertension.Metabolites · 2022Review
- Targeting ProteinCells · 2022Review
- Hyaluronan: Metabolism and Function.Biomolecules · 2020Review
- Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease.Biomedicines · 2020Review
- Enhanced hexosamine metabolism drives metabolic and signaling networks involving hyaluronan production and O-GlcNAcylation to exacerbate breast cancer.Cell death & disease · 2019Article
- O-GlcNAcylation in immunity and inflammation: An intricate system (Review).International journal of molecular medicine · 2019Review
- Inhibition of the hexosamine biosynthesis pathway potentiates cisplatin cytotoxicity by decreasing BiP expression in non-small-cell lung cancer cells.Molecular carcinogenesis · 2019Article
- Rho-kinase inhibitor Y-27632 and hypoxia synergistically enhance chondrocytic phenotype and modify S100 protein profiles in human chondrosarcoma cells.Scientific reports · 2017Article
- YY1 directly suppresses MYCT1 leading to laryngeal tumorigenesis and progress.Cancer medicine · 2017Article
- Article
- A Trickster in Disguise: Hyaluronan's Ambivalent Roles in the Matrix.Frontiers in oncology · 2017Review
- UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression.Cellular and molecular life sciences : CMLS · 2016Article
- 4-Methylumbelliferone Diminishes Catabolically Activated Articular Chondrocytes and Cartilage Explants via a Mechanism Independent of Hyaluronan Inhibition.The Journal of biological chemistry · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Hyaluronan, a high molecular mass polysaccharide on the vertebrate cell surface and extracellular matrix, is produced at the plasma membrane by hyaluronan synthases using UDP-GlcNAc and UDP-GlcUA as substrates. The availability of these UDP-sugar substrates can limit the synthesis rate of hyaluronan. In this study, we show that the cellular level of UDP-HexNAc also controls hyaluronan synthesis by modulating the expression of HAS2 (hyaluronan synthase 2). Increasing UDP-HexNAc in HaCaT keratinocytes by adding glucosamine down-regulated HAS2 gene expression, whereas a decrease in UDP-HexNAc, realized by mannose treatment or siRNA for GFAT1 (glutamine:fructose-6-phosphate amidotransferase 1), enhanced expression of the gene. Tracing the UDP-HexNAc-initiated signal to the HAS2 promoter revealed no change in the binding of STAT3, NF-κB, and cAMP response element-binding protein, shown previously to mediate growth factor and cytokine signals on HAS2 expression. Instead, altered binding of SP1 and YY1 to the promoter correlated with cellular UDP-HexNAc content and inhibition of HAS2 expression. siRNA silencing of YY1 and SP1 confirmed their inhibitory effects on HAS2 expression. Reduced and increased levels of O-GlcNAc-modified SP1 and YY1 proteins were associated with stimulation or inhibition of HAS2 expression, respectively. Our data are consistent with the hypothesis that, by regulating the level of protein O-GlcNAc modifications, cellular UDP-HexNAc content controls HAS2 transcription and decreases the effects on hyaluronan synthesis that would result from cellular fluctuations of this substrate.
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Registered trials
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