Detection of phosphorylation signatures specific to cancer-related PI3-Kinase isoforms p110α and p110β

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buir.advisorÇizmecioğlu, Onur
dc.contributor.authorSulaiman, Mahnoor
dc.date.accessioned2023-03-02T11:45:44Z
dc.date.available2023-03-02T11:45:44Z
dc.date.copyright2023-01
dc.date.issued2023-01
dc.date.submitted2023-02-03
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (Master's): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2023.en_US
dc.descriptionIncludes bibliographical references (leaves 113-121).en_US
dc.description.abstractThe PI3K signaling pathway is required for many physiological activities, but it is commonly disrupted during cancer formation. The PI3K p110α and βisoforms, encoded by the PIK3CA and PIK3CB genes, are lipid kinases that phosphorylate PIP2 to PIP3 to activate the PI3K pathway. However, the distinct molecular targets of these isoforms have yet to be discovered, making targeted treatment problematic. According to cancer genomics research, the PIK3CA gene is commonly altered in cancers, but the PIK3CB gene is frequently amplified. The clinical usage of Pan-PI3K inhibitors has resulted in significant side effects, prompting the development of isoform-specific inhibitors. However, it has been shown that these drugs trigger alternate signaling systems downstream, leading in resistance to single-agent treatment. Our research intends to uncover distinctive protein-protein interactions of PI3K isoforms, as well as the consequent different phospho-proteomic signatures, which might be crucial determinants of specific cellular activities. This will be accomplished by using isogenic MEF cells that are only dependent on the p110α or p110β isoforms, isoform-specific pharmacological inhibitors BYL-719 and KIN 193, and a high-resolution mass spectrometry-based method to determine the phosphorylation levels of these protein samples. The predictive biomarkers discovered in this study can be utilized to identify patients who will benefit from PI3K-targeted drugs and to better understand the resistance mechanisms that may arise in response to pathway inhibition.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2023-03-02T11:45:44Z No. of bitstreams: 1 B161769.pdf: 5158476 bytes, checksum: 832e98739a71b87bd8a68e43850f2b53 (MD5)en
dc.description.provenanceMade available in DSpace on 2023-03-02T11:45:44Z (GMT). No. of bitstreams: 1 B161769.pdf: 5158476 bytes, checksum: 832e98739a71b87bd8a68e43850f2b53 (MD5) Previous issue date: 2023-01en
dc.description.statementofresponsibilityby Mahnoor Sulaimanen_US
dc.embargo.release2023-08-02
dc.format.extent123 leaves : color illustrations, color charts ; 30 cm.en_US
dc.identifier.itemidB161769
dc.identifier.urihttp://hdl.handle.net/11693/112021
dc.language.isoEnglishen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectPI3K signallingen_US
dc.subjectPIK3CA isoformen_US
dc.subjectPIK3CB isoformen_US
dc.subjectPhosphoproteomicsen_US
dc.subjectBYL719en_US
dc.subjectKIN193en_US
dc.subjectCanceren_US
dc.subjectResistanceen_US
dc.subjectMass spectrometryen_US
dc.subjectIMACen_US
dc.subjectPhosphorylationen_US
dc.titleDetection of phosphorylation signatures specific to cancer-related PI3-Kinase isoforms p110α and p110βen_US
dc.title.alternativeKanserle ilişkili PI3-Kinase p110α ve p110β izoformalarına özel fosforilasyon imzalarının belirlenmesien_US
dc.typeThesisen_US
thesis.degree.disciplineMolecular Biology and Genetics
thesis.degree.grantorBilkent University
thesis.degree.levelMaster's
thesis.degree.nameMS (Master of Science)

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