Приказ основних података о дисертацији

Bioinformatic and glycobiochemical analysis of human CA125 antigen modular organization

dc.contributor.advisorKorać, Aleksandra
dc.contributor.otherKorać, Aleksandra
dc.contributor.otherJanković, Miroslava
dc.contributor.otherJanković, Miroslava
dc.contributor.otherMilutinović, Bojana
dc.creatorMitić, Ninoslav M.
dc.date.accessioned2016-01-05T11:46:44Z
dc.date.available2016-01-05T11:46:44Z
dc.date.available2020-07-03T08:09:25Z
dc.date.issued2012-11-09
dc.identifier.urihttps://nardus.mpn.gov.rs/handle/123456789/2088
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=49
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:3035/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=1024527282
dc.description.abstractCА125 antigen, poznat kao marker seroznog karcinoma ovarijuma, predstavlja ekstracelularni deo mucina 16 (MUC16), koji nastaje njegovom proteolitiĉkom degradacijom. МUC16 pripada grupi transmembranskih proteina tipa I, i eksprimiran je u velikom broju embrionalnih, ali i adultnih tkiva. Njegovu primarnu strukturu karakteriše prisustvo tri regiona: N-terminalni region i region tandemskih ponovaka, koji su smešteni ekstracelularno, i C-terminalni region, koji se sastoji od transmembranskog dela i kratkog citoplazmatskog repa. Ekstracelularni region je intenzivno glikozilovan, a u intracelularnom regionu se nalazi potencijalno mesto fosforilacije. Fosforilacija predstavlja signal za proteolizu i oslobaĊanje ekstracelularnog dela molekula (СА125 antigen), koji se kao takav može detektovati u razliĉitim telesnim teĉnostima. Biološka uloga MUC16/CA125, još uvek nije razjašnjena. Dosadašnja ispitivanja funkcije MUC16 (membranska forma) su, uglavnom, bila bazirana na in vitro model sistemu ćelija ovarijalnog karcinoma, dok su literaturni podaci o aktivnosti CA125 antigena (solubilna forma) veoma retki. Solubilna forma predstavlja funkcionalni analog i kompetitor membranskoj formi i, u cirkulaciji, ona prva dospeva u kontakt sa razliĉitim tipovima normalnih ili patološki izmenjenih ćelija, ali ne postoje eksperimentalni dokazi o mogućem uticaju na njihovu adhezivnost, kao i imunomodulatorna svojstva. U ovom radu je ispitivana modularna organizacija MUC16/CA125 na bioinformatiĉkom i glikobiohemijskom nivou, sa ciljem da se bliže definišu biološki kapacitet i posebnosti prezentacije ovog molekula u kontekstu interaktoma ĉoveka. Bioinformatiĉka analiza, kao deo strategije za otkrivanje moguće biološke uloge MUC16/CA125, do sada nije korišćena u ispitivanjima ovog antigena. Pored toga, u kontekstu diskretnih bioloških funkcija, bez obzira na izuzetan biomedicinski znaĉaj, ne postoje eksperimentalni podaci o interakcijama MUC16/CA125 sa specifiĉnim klasama receptora na ćelijama krvnog sistema.CА125 antigen, poznat kao marker seroznog karcinoma ovarijuma, predstavlja ekstracelularni deo mucina 16 (MUC16), koji nastaje njegovom proteolitiĉkom degradacijom. МUC16 pripada grupi transmembranskih proteina tipa I, i eksprimiran je u velikom broju embrionalnih, ali i adultnih tkiva. Njegovu primarnu strukturu karakteriše prisustvo tri regiona: N-terminalni region i region tandemskih ponovaka, koji su smešteni ekstracelularno, i C-terminalni region, koji se sastoji od transmembranskog dela i kratkog citoplazmatskog repa. Ekstracelularni region je intenzivno glikozilovan, a u intracelularnom regionu se nalazi potencijalno mesto fosforilacije. Fosforilacija predstavlja signal za proteolizu i oslobaĊanje ekstracelularnog dela molekula (СА125 antigen), koji se kao takav može detektovati u razliĉitim telesnim teĉnostima. Biološka uloga MUC16/CA125, još uvek nije razjašnjena. Dosadašnja ispitivanja funkcije MUC16 (membranska forma) su, uglavnom, bila bazirana na in vitro model sistemu ćelija ovarijalnog karcinoma, dok su literaturni podaci o aktivnosti CA125 antigena (solubilna forma) veoma retki. Solubilna forma predstavlja funkcionalni analog i kompetitor membranskoj formi i, u cirkulaciji, ona prva dospeva u kontakt sa razliĉitim tipovima normalnih ili patološki izmenjenih ćelija, ali ne postoje eksperimentalni dokazi o mogućem uticaju na njihovu adhezivnost, kao i imunomodulatorna svojstva. U ovom radu je ispitivana modularna organizacija MUC16/CA125 na bioinformatiĉkom i glikobiohemijskom nivou, sa ciljem da se bliže definišu biološki kapacitet i posebnosti prezentacije ovog molekula u kontekstu interaktoma ĉoveka. Bioinformatiĉka analiza, kao deo strategije za otkrivanje moguće biološke uloge MUC16/CA125, do sada nije korišćena u ispitivanjima ovog antigena. Pored toga, u kontekstu diskretnih bioloških funkcija, bez obzira na izuzetan biomedicinski znaĉaj, ne postoje eksperimentalni podaci o interakcijama MUC16/CA125 sa specifiĉnim klasama receptora na ćelijama krvnog sistema.In silico analiza modularne organizacije MUC16/CA125, vršena je na osnovu podataka koji su preuzeti sa UniProtKB baze podataka, a koji se odnose na molekul izolovan iz ćelijske linije ovarijalnog karcinoma ĉoveka, OVCAR-3. Bioinformatiĉka analiza je obuhvatila: odreĊivanje homologije (korišćenjem BLAST, Basic Local Alignment Search Tool alatke); ispitivanje prisustva obrazaca, strukturnih motiva i konzerviranih domena (korišćenjem baza podataka kao što su Bgee: a dataBase for Gene Expression Evolution i Gene Ontology, CDD, ELM, BLOCKS, InterProScan, MyHits i iProClass); odreĊivanje fiziĉko-hemijskih osobina, globularnosti i odstupanja od pretpostavljene tercijarne strukture (korišćenjem ProtParam, ProtScale i GLOBPLOT v2.3 alatki); i predviĊanje funkcije pomoću alatki koje koriste nekoliko programa: JAFA, ProtFun 2.2 i GeneOntology. Glikobiohemijska analiza je obuhvatila ispitivanje uticaja CA125 antigena na adhezivnost i agregabilnost eritrocita, kao i moguće interakcije sa razliĉitim tipovima leukocitnih lektina tj. sigleka (Siglec - sialic acid-binding immunogobulin (Ig)-like lectin) i receptora sliĉnih lektinima tipa C (selektini, DC-SIGN - dendritic cell-specific ICAM-3-grabbing non-integrin 1, MMR - macrophage mannose receptor). Ispitivanje efekta CA125 antigena na eritrocite ĉoveka odreĊivano je u testovima na ĉvrstoj fazi ili primenom svetlosne mikroskopije. Interakcija CA125 antigena sa leukocitnim receptorima ispitivana je pomoću lektinskog- i imunoblota, kao i u testovima vezivanja i inhibicije na ĉvrstoj fazi, sa imobilisanim antigenima. Glikobiohemijskom analizom su, pored antigena iz ćelijske linije ovarijalnog karcinoma ĉoveka (clCA125), bili obuhvaćeni i antigen kancerskog porekla iz pleuralne teĉnosti (pfCA125) kao i antigen fetalnog porekla (pCA125), koji se sintetiše tokom trudnoće. Rezultati in silico analize proteinske sekvence MUC16/CA125, stavili su ovaj molekul u kontekst modularnih proteina sa anotiranom ulogom u adheziji i srodnim procesima. Uvid u sekvence koje pokazuju sliĉnost sa sekvencom MUC16/CA125, pokazao je da se one, uglavnom, nalaze u ekstracelularnom regionu MUC16, koji je bogat serinom i treoninom. Ove sliĉnosti se nisu mogle povezati sa anotiranim domenima iz dostupnih baza podataka, osim parcijalno, ali statistiĉki znaĉajno sa BLLF1, multidomenom karakteristiĉnim za glikoproteine omotaĉa virusa iz familije Herpesviridae. Bioinformatiĉka analiza je ukazala i na moguću korelaciju funkcionalnih aktivnosti, koje se pripisuju domenima bogatim serinom/treoninom kod identifikovanih proteina u okviru ispitivanih taksona, i moguće funkcije CA125 antigena. Na osnovu dobijenih rezultata, uloga CA125 antigena u procesima adhezije bi mogla ukljuĉiti i interakcije posredstvom konzerviranih proteinskih sekvenci, odgovornih za jonski transport, i interakcije sa šećernim supstratima. Polazeći od mucinske prirode CA125 antigena, kao i fizioloških stanja u kojima je njegova koncentracija u serumu povećana, u prvom delu glikobiohemijske analize, ispitan je uticaj CA125 antigena na eritrocite ĉoveka. Dobijeni rezultati su ukazali da pCA125 i pfCA125 umereno povećavaju agregaciju eritrocita, i uspešno inhibiraju njihovu adheziju. Za razliku od njih, clCA125 je pokazao neznatan uticaj na modulaciju ovih osobina eritrocita. Sumarni rezultati drugog dela analize, koja se odnosila na interakcije sa leukocitnim receptorima, pokazali su da CA125, kao ligand, može stupiti u interakcije sa razliĉitim tipovima proteina koji vezuju sijalinsku kiselinu. Pokazano je da postoje specifiĉni obrasci vezivanja sigleka za ispitivane CA125 antigene, kojima se ovi antigeni, uspešnije, razlikuju u odnosu na njihovo poreklo, nego što se to ĉini na osnovu obrazaca vezivanja biljnih lektina, takoĊe specifiĉnih za sijalinsku kiselinu. Najuoĉljivija razlika je zapažena u odnosu na ligandni kapacitet CA125 antigena fetalnog porekla prema sigleku-7, prisutnom na dendritskim ćelijama, NK (natural killer cell) ćelijama, monocitima i CD8+ T ćelijama i clCA125 antigena kancerskog porekla prema sigleku-9 i sigleku-10, prisutnim na B ćelijama, NK ćelijama, monocitima, neutrofilima i CD8+ T ćelijama. Za razliku od sigleka, sva tri ispitivana selektina: L-selektin, E-selektin i P-selektin su, na dozno-zavisan naĉin, interagovali sa pfCA125 i u manjoj meri pCA125, ali ne i clCA125. Pored toga, zapaženo je i da je P-selektin reagovao na znatno nižim koncentracijama nego L- i E-selektin. Na osnovu uoĉenog visokog afiniteta P-selektina, CA125 antigen bi pre stupio u interakcije sa aktiviranim endotelnim ćelijama ili krvnim ploĉicama, na kojima je ovaj selektin prisutan, nego sa ćelijama na kojima su prisutni drugi tipovi selektina. Ispitivanje interakcije CA125 antigena i DC-SIGN, koji je eksprimiran na površini dendritskih ćelija (DC) i koji vezuje manan i visoko-manozne glikane kao i glikane sa terminalnim Lex/Ley/Lea/Leb antigenima, pokazalo je da on prepoznaje pCA125 i pfCA125 antigen. Rezultati inhibicije su ukazali da je vezivanje DC-SIGN za pCA125 zavisno od prisustva glikana bogatih manozom, za razliku od vezivanja pfCA125, koje je nezavisno od prisustva N- ili O-glikana, što bi moglo uticati na njegove diskretne receptorske funkcije. Manozni receptor makrofaga (MMR), koji je prisutan na makrofagama i DC i koji vezuje terminalnu manozu i fukozu i SLex, nije reagovao ni sa jednim od ispitivanih CA125 antigena. Receptori sliĉni lektinima tipa C imaju važnu ulogu u imunskom sistemu, u smislu posredovanja u interakcijama tipa ćelija-ćelija, tj. u meĊusobnom kontaktu leukocita ili u njihovom kontaktu sa endotelom, kao i u vezivanju patogena. Promene u glikozilaciji liganada za receptore sliĉne lektinima tipa C, direktno utiĉu na njihovu aktivnost i specifiĉnost i imaju važne posledice na razvoj, preživljavanje i reaktivnost ćelija krvnog i imunskog sistema. Rezultati ovoga rada ukazuju da bi razlike u strukturi/glikozilaciji CA125 antigena, koje se vezuju za posebna fiziološka i patološka stanja, mogle menjati njegov uticaj na ćelije krvnog sistema ĉoveka i imati znaĉajne biomedicinske posledice u razliĉitim mikrosredinama. Dalji uvid u prirodu i mehanizme multifunkcionalnosti CA125 antigena zahteva interdisciplinarni pristup baziran na kompleksnim interakcijama koje su posredovane razliĉitim strukturnim domenima.sr
dc.description.abstractCA125 antigen, a well known tumour marker for serous ovarian cancer, is an extracellular part of the mucin 16 (MUC16) molecule. This antigen arises from proteolytic degradation of MUC16, a type I transmembrane protein, expressed in both embrional and adult tissue. The primary structure of MUC16 consists of three characteristic parts: an N-terminal region and a series of tandem repeats, which are located extracellularly, and a C-terminal region, which consists of the transmembrane part and a short cytoplasmic tail. The extracellular peptide is extensively glycosylated, and there is a potential phosphorylation site in the intracellular chain. Phosphorylation is a signal for proteolysis and release of the extracellular part of the molecule (CA125 antigen), which can be detected as such in various body fluids. The biological role of MUC16/CA125 is not yet understood. Previous investigations of MUC16 (membrane form) functions were generally based on in vitro cell model systems of ovarian cancer, whereas published data on the activity of CA125 antigen (soluble form) are very rare. The soluble form is a functional analog and competitor to the membrane form, and, in the circulation, it first contacts different types of normal or pathologically altered cells. However, there is no experimental evidence on its possible impact on their adhesion nor immunomodulatory properties. In this work, the modular organization of human CA125 antigen was analyzed bioinformatically and glycobiochemically, aiming at closer definition of the biological capacity and presentation of this molecule in the context of the human interactome. As part of a strategy to detect a possible biological role for MUC16/CA125, bioinformatics analysis has never been used in studies of this antigen. In addition, in the context of discrete biological functions, regardless of its great biomedical importance, there are no CA125 antigen, a well known tumour marker for serous ovarian cancer, is an extracellular part of the mucin 16 (MUC16) molecule. This antigen arises from proteolytic degradation of MUC16, a type I transmembrane protein, expressed in both embrional and adult tissue. The primary structure of MUC16 consists of three characteristic parts: an N-terminal region and a series of tandem repeats, which are located extracellularly, and a C-terminal region, which consists of the transmembrane part and a short cytoplasmic tail. The extracellular peptide is extensively glycosylated, and there is a potential phosphorylation site in the intracellular chain. Phosphorylation is a signal for proteolysis and release of the extracellular part of the molecule (CA125 antigen), which can be detected as such in various body fluids. The biological role of MUC16/CA125 is not yet understood. Previous investigations of MUC16 (membrane form) functions were generally based on in vitro cell model systems of ovarian cancer, whereas published data on the activity of CA125 antigen (soluble form) are very rare. The soluble form is a functional analog and competitor to the membrane form, and, in the circulation, it first contacts different types of normal or pathologically altered cells. However, there is no experimental evidence on its possible impact on their adhesion nor immunomodulatory properties. In this work, the modular organization of human CA125 antigen was analyzed bioinformatically and glycobiochemically, aiming at closer definition of the biological capacity and presentation of this molecule in the context of the human interactome. As part of a strategy to detect a possible biological role for MUC16/CA125, bioinformatics analysis has never been used in studies of this antigen. In addition, in the context of discrete biological functions, regardless of its great biomedical importance, there are no experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains of experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains of experimental data on the interactions of MUC16/CA125 with specific classes of receptors on cells of the blood system. The modular organization of MUC16/CA125, was analyzed in silico using data taken from the UniProtKB database, which refers to a molecule isolated from the human ovarian cancer cell line, OVCAR-3. Bioinformatic analysis included: determination of homology (using BLAST, Basic Local Alignment Search Tool Tool); investigation of patterns, structural motifs and conserved domains (using databases such as Bgee: a database for Gene Expression and Gene Ontology Evolution, CDD, ELM, BLOCKS, InterProScan and MyHits iProClass); determination of physical and chemical properties, globularity and deviations from the assumed tertiary structure (using ProtParam, ProtScale and GLOBPLOT v2.3 tools); and function prediction using tools that employ several programs: JAFA, ProtFun 2.2 and GeneOntology. Glycobiochemical analysis comprised examination of the influence of CA125 on adhesion and aggregation of erythrocytes, as well as on interactions with different types of leukocyte lectins, namely siglecs [sialic acid-binding immunogobulin (Ig)-like lectin] and C-type lectin-like receptors [selectins, dendritic cell-specific ICAM-3-grabbing non-integrin 1 (DC-SIGN) and macrophage mannose receptor (MMR)]. The effect of CA125 antigen on human erythrocytes was determined using solid phase tests and light microscopy. The interaction of CA125 with leukocyte receptors was investigated employing lectin-blot and immunoblot, as well as binding and inhibition solid phase assays. Cancer antigen isolated from human pleural fluid (pfCA125) and pregnancy-associated antigen (pCA125) were included in the glycobiochemical analysis in addition to antigen from the human ovarian carcinoma cell line (clCA125). The results of in silico analysis placed MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes. They pointed to similarities within extracellular serine/threonine rich regions of MUC16 to protein sequences expressed in evolutionarily distant taxa. No relation to annotated domains from available databases appeared, except for BLLF1, a multidomain characteristic of virus envelope glycoproteins of the Herpesviridae family. Bioinformatics analysis also pointed to a possible correlation between functional activities, which are attributed to serine/threonine rich domains ofproteins identified in the studied taxa, and possible CA125 antigen function. Based on these results, the role of CA125 antigen in adhesion processes could involve interactions through conserved protein sequences responsible for ion transport, and for interactions with sugar substrates. Considering the mucin nature of CA125 antigen, as well as physiological conditions in which its concentration in serum is increased, the effect of this antigen on human erythrocytes was investigated in the first part of glycobiochemical analysis. The results showed that pCA125 and pfCA125 moderately increased aggregation of erythrocytes, and successfully inhibited their adhesion. In contrast, clCA125 showed little to no modulation of these properties. The second part of the glycobiochemical analysis related to interactions with leukocyte receptors. This showed that, as a ligand, CA125 may interact with different types of proteins that bind sialic acid. Siglecs were found to have specific binding patterns, which more effectively distinguished CA125 antigens of fetal from those of cancer origin, in contrast to the binding patterns of sialic acid-specific plant lectins. The most obvious difference was the ligand capacity of pCA125 antigen towards siglec-7, expressed on dendritic cells, NK (natural killer cells), monocytes and CD8+ T cells, and clCA125 towards siglec-9 and siglec-10 on B cells, NK cells, monocytes, neutrophils and CD8+ T cells. Unlike siglecs, all three investigated selectins: L-selectin, E-selectin and P-selectin, interacted in a dose-dependent manner with pfCA125, and to a lesser extent with pCA125, but not with clCA125. Moreover, P-selectin reacted at significantly lower concentrations than L- or E-selectin. Thus, CA125 antigen would preferentially interact with activated endothelial cells or platelets expressing P-selectin, compared to cells expressing the other types of selectin. The interaction of CA125 antigen and DC-SIGN, which is specific for mannan, high-mannose glycans and glycans with terminal Lex / Ley / Lea / Leb antigens was studied. DC-SIGN is expressed on dendritic cells (DC) and recognized pCA125 and pfCA125 antigen. Inhibition of DC-SIGN binding to pCA125 was dependent on the presence of mannose-rich glycans, in contrast to the binding to pfCA125, which was not affected by the presence of N- or O-linked glycans, all which can modify their discrete receptor functions. Macrophage mannose receptor (MMR), which is expressed on macrophages and DC, and which binds terminal mannose, fucose and sialyl Lex, did not react with any of the tested CA125 antigens. C-type lectin-like receptors play an important role in the immune system, mediating in cell-cell interactions, i.e. contacts between leukocytes or between leukocytes and endothelium,and in the binding of pathogens. Glycosylation changes in ligands for C-type lectin-like receptors directly influence their activity and specificity and have important effects on the development, survival and reactivity of cells of the blood and immune systems. Based on the results of this study, differences in the structure/glycosylation of CA125 antigens associated with different physiological or pathological conditions, could alter their influence on the human blood cells, and have important biomedical implications in different microenvironments. Further insight into the nature and mechanisms of CA125 multifunctionality requires an interdisciplinary approach, based on complex interactions that are mediated by its different structural domains.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Биолошки факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173010/RS//
dc.rightsopenAccessen
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceУниверзитет у Београдуsr
dc.subjectCA125 antigensr
dc.subjectCA125 antigenen
dc.subjectin silico analizasr
dc.subjectglikobiohemijska analizasr
dc.subjecteritrocitisr
dc.subjectadhezijasr
dc.subjectleukocitni receptorisr
dc.subjectsiglecisr
dc.subjectselektinisr
dc.subjectDC-SIGNsr
dc.subjectmanozni receptor makrofagasr
dc.subjectin silico analysisen
dc.subjectglycobiochemical analysisen
dc.subjecterythrocytesen
dc.subjectadhesionen
dc.subjectleukocyte receptorsen
dc.subjectsiglecsen
dc.subjectselectinsen
dc.subjectDC-SIGNen
dc.subjectmacrophage mannose receptoren
dc.titleBioinformatička i glikobiohemijska analiza modularne organizacije CA125 antigena čovekasr
dc.titleBioinformatic and glycobiochemical analysis of human CA125 antigen modular organizationen
dc.typedoctoralThesisen
dc.rights.licenseBY-NC-ND
dcterms.abstractКораћ, Aлександра; Милутиновић, Бојана; Јанковић, Мирослава; Јанковић, Мирослава; Кораћ, Aлександра; Митић, Нинослав М.; Биоинформатичка и гликобиохемијска анализа модуларне организације ЦA125 антигена човека; Биоинформатичка и гликобиохемијска анализа модуларне организације ЦA125 антигена човека;
dc.identifier.fulltexthttps://nardus.mpn.gov.rs/bitstream/id/2086/Disertacija.pdf
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/2086/Disertacija.pdf
dc.identifier.doi10.2298/bg20121109mitic
dc.identifier.rcubhttps://hdl.handle.net/21.15107/rcub_nardus_2088


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