Uloga proteina deltaNp73alfa u senescenciji izazvanoj oštećenjem DNA u normalnim i tumorskim stanicama čovjeka

master's thesis

• Title (english): The role of deltaNp73alpha protein in DNA damage-induced senescence in normal and cancer human cells
• Author: Marina Katić
• Mentor: Anđela Horvat (mentor)
• Committee member: Morana Dulić (predsjednik povjerenstva)
• Committee member: Iva Juranović Cindrić (član povjerenstva)
• Committee member: Željka Soldin (član povjerenstva)
• Committee member: Marko Močibob (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2021-02-23, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Stanična senescencija je trajni izlazak stanica iz ciklusa do kojeg dolazi zbog skraćivanja telomera, aktivacije onkogena i oštećenja DNA. Protein p73 (član obitelji proteina p53) ima niz uloga u odgovoru na oštećenje DNA, a njegova uloga u tumorigenezi je složena. Postoje mnogobrojne izoforme proteina p73 svrstane u dvije glavne skupine: TAp73 i ΔNp73. Potaknuti potencijalnim onkogenim djelovanjem izoforme ΔNp73α ispitali smo njezin utjecaj na ulazak stanica u senescenciju izazvanu oštećenjem DNA γ-zračenjem u normalnim fibroblastima i staničnoj liniji osteosarkoma čovjeka. Senescentne stanice detektirane su praćenjem endogene β-galaktozidazne aktivnosti povezane sa starenjem, pri čemu je pojačana ekspresija ΔNp73α dovela do umjerenog porasta udjela senescentnih stanica. Metodom Western hibridizacije ispitana je ekspresija proteina uključenih u regulaciju staničnog ciklusa nakon oštećenja DNA, a dobiveni rezultati ukazuju na višu ekspresiju markera stanične proliferacije pod utjecajem ΔNp73α. Dobiveni rezultati predstavljaju vrijednu podlogu za buduća istraživanja uloge izoforme ΔNp73α u tumorigenezi.

Abstract (english)

Cellular senescence is permanent cell cycle exit caused by telomere shortening, oncogene activation and DNA damage. P73 protein (a p53 protein family member) has different functions in DNA damage response, and its role in tumorigenesis is complex. There are multiple p73 protein isoforms divided into two main groups: TAp73 and ΔNp73. Encouraged by potentially oncogenic activity of ΔNp73α isoform, we investigated its impact on senescence onset after DNA damage induced by γ-irradiation in normal human fibroblasts and osteosarcoma cell line. Senescent cells were detected by analysis of endogenous senescence associated β-galactosidase activity, showing moderate increase in the frequency of senescence in cells overexpressing ΔNp73α. Expression of proteins involved in cell cycle regulation after DNA damage was analyzed by Western blot, suggesting higher expression of the markers of cellular proliferation caused by overexpression of ΔNp73α. These results represent a valuable basis for future investigation of the ΔNp73α role in tumorigenesis.

• Keywords: ΔNp73; kontrola staničnog ciklusa; oštećenje DNA molekule; senescencija
• Keywords (english): ΔNp73α; cell cycle control; DNA damage; senescence
• Language: croatian
• URN:NBN: urn:nbn:hr:217:111798
• Project: Number: IP-2016-06-4021; Title: Struktura, funkcija i evolucija proteina Nme6/Nm23-H6; Acronym: Nemo6; Leader: Maja Herak-Bosnar; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: IP
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-02-23
• Created on: 2021-03-18 12:23:36