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dc.contributor.authorSiiskonen, Hanna
dc.contributor.authorOikari, Sanna
dc.contributor.authorPasonen-Seppänen, Sanna
dc.contributor.authorRilla, Kirsi
dc.date.accessioned2016-05-11T06:51:47Z
dc.date.available2016-05-11T06:51:47Z
dc.date.issued2015-02-05
dc.identifier10.3389/fimmu.2015.00043
dc.identifier.citationSiiskonen H, Oikari S, Pasonen-Seppänen S and Rilla K (2015) Hyaluronan synthase 1: a mysterious enzyme with unexpected functions. Front. Immunol. 6:43. doi: 10.3389/fimmu.2015.00043fi_FI
dc.identifier.issn1664-3224
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/38
dc.descriptionArticle
dc.description.abstractHyaluronan synthase 1 (HAS1) is one of three isoenzymes responsible for cellular hyaluronan synthesis. Interest in HAS1 has been limited because its role in hyaluronan production seems to be insignificant compared to the two other isoenzymes, HAS2 and HAS3, which have higher enzymatic activity. Furthermore, in most cell types studied so far, the expression of its gene is low and the enzyme requires high concentrations of sugar precursors for hyaluronan synthesis, even when overexpressed in cell cultures. Both expression and activity of HAS1 are induced by pro-inflammatory factors like interleukins and cytokines, suggesting its involvement in inflammatory conditions. Has1 is upregulated in states associated with inflammation, like atherosclerosis, osteoarthritis, and infectious lung disease. In addition, both full length and splice variants of HAS1 are expressed in malignancies like bladder and prostate cancers, multiple myeloma, and malignant mesothelioma. Interestingly, immunostainings of tissue sections have demonstrated the role of HAS1 as a poor predictor in breast cancer, and is correlated with high relapse rate and short overall survival. Utilization of fluorescently tagged proteins has revealed the intracellular distribution pattern of HAS1, distinct from other isoenzymes. In all cell types studied so far, a high proportion of HAS1 is accumulated intracellularly, with a faint signal detected on the plasma membrane and its protrusions. Furthermore, the pericellular hyaluronan coat produced by HAS1 is usually thin without induction by inflammatory agents or glycemic stress and depends on CD44–HA interactions. These specific interactions regulate the organization of hyaluronan into a leukocyte recruiting matrix during inflammatory responses. Despite the apparently minor enzymatic activity of HAS1 under normal conditions, it may be an important factor under conditions associated with glycemic stress like metabolic syndrome, inflammation, and cancer.fi_FI
dc.language.isoenfi_FI
dc.publisherFrontiers Media SAfi_FI
dc.relation.ispartofseriesFrontiers in Immunology
dc.relation.urihttps://doi.org/10.3389/fimmu.2015.00043
dc.rightsCC BY 4.0 https://creativecommons.org/licenses/by/4.0/
dc.subjecthyaluronanfi_FI
dc.subjecthyaluronan synthasefi_FI
dc.subjectCD44fi_FI
dc.subjectinflammationfi_FI
dc.subjectcytokinesfi_FI
dc.subjectcancerfi_FI
dc.titleHyaluronan synthase 1 : a mysterious enzyme with unexpected functionsfi_FI
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.description.versionPublisher's pdf
dc.contributor.departmentTerveystieteiden tiedekunta
uef.solecris.id32726890
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Authors
dc.relation.doi10.3389/fimmu.2015.00043
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.relation.articlenumber43
dc.relation.issn1664-3224
dc.relation.volume6
dc.rights.accesslevelopenAccess


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