Show simple item record

dc.contributor.authorEl Jellas, Khadijaen_US
dc.contributor.authorJohansson, Bente Bergen_US
dc.contributor.authorFjeld, Karianneen_US
dc.contributor.authorAntonopoulos, Aristotelisen_US
dc.contributor.authorImmervoll, Heikeen_US
dc.contributor.authorChoi, Man Hungen_US
dc.contributor.authorHoem, Dagen_US
dc.contributor.authorLowe, Mark E.en_US
dc.contributor.authorLombardo, Dominiqueen_US
dc.contributor.authorNjølstad, Pål Rasmusen_US
dc.contributor.authorDell, Anneen_US
dc.contributor.authorMas, Ericen_US
dc.contributor.authorHaslam, Stuart M.en_US
dc.contributor.authorMolven, Andersen_US
dc.date.accessioned2019-02-21T13:10:29Z
dc.date.available2019-02-21T13:10:29Z
dc.date.issued2018
dc.identifier.issn0021-9258
dc.identifier.urihttps://hdl.handle.net/1956/19132
dc.descriptionPostponed access: the file will be accessible after 2019-10-13en_US
dc.description.abstractCarboxyl-ester lipase (CEL) is a pancreatic fat-digesting enzyme associated with human disease. Rare mutations in the CEL gene cause a syndrome of pancreatic exocrine and endocrine dysfunction denoted MODY8, whereas a recombined CEL allele increases the risk for chronic pancreatitis. Moreover, CEL has been linked to pancreatic ductal adenocarcinoma (PDAC) through a postulated oncofetal CEL variant termed feto-acinar pancreatic protein (FAPP). The monoclonal antibody mAb16D10 was previously reported to detect a glycotope in the highly O-glycosylated, mucin-like C terminus of CEL/FAPP. We here assessed the expression of human CEL in malignant pancreatic lesions and cell lines. CEL was not detectably expressed in neoplastic cells, implying that FAPP is unlikely to be a glycoisoform of CEL in pancreatic cancer. Testing of the mAb16D10 antibody in glycan microarrays then demonstrated that it recognized structures containing terminal GalNAc- 1,3(Fuc- 1,2)Gal (blood group A antigen) and also repeated protein sequences containing GalNAc residues linked to Ser/Thr (Tn antigen), findings that were supported by immunostainings of human pancreatic tissue. To examine whether the CEL glycoprotein might be modified by blood group antigens, we used high-sensitivity MALDI-TOF MS to characterize the released O-glycan pool ofCELimmunoprecipitatedfromhumanpancreatic juice. We found that the O-glycome of CEL consisted mainly of core 1/core 2 structures with a composition depending on the subject’s FUT2 and ABO gene polymorphisms. Thus, among digestive enzymes secreted by the pancreas,CELis a glycoprotein with some unique characteristics, supporting the view that it could serve additional biological functions to its cholesteryl esterase activity in the duodenum.en_US
dc.language.isoengeng
dc.publisherThe American Society for Biochemistry and Molecular Biologyeng
dc.rightsThis research was originally published in the Journal of Biological Chemistry. El Jellas et al. The mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinants. J. Biol. Chem. 2018; 293(50):19476-19491. © the Author(s).eng
dc.titleThe mucinous domain of pancreatic carboxyl-ester lipase (CEL) contains core 1/core 2 O-glycans that can be modified by ABO blood group determinantsen_US
dc.typePeer reviewed
dc.typeJournal article
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2018 El Jellas et al.
dc.identifier.doihttps://doi.org/10.1074/jbc.ra118.001934
dc.identifier.cristin1678800
dc.source.journalJournal of Biological Chemistry
dc.source.40293
dc.source.1450
dc.source.pagenumber19476-19491


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record