Uloga proteina FADD u regulaciji stanične smrti

doctoral thesis

• Title (english): The role of FADD protein in cell death
• Author: Maja Antunović
• Mentor: Inga Marijanović (mentor)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Maja Osmak (član povjerenstva)
• Committee member: Vera Garaj-Vrhovac (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2014, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology
• Universal decimal classification (UDC): 577 - Biochemistry. Molecular biology. Biophysics

Abstract

Vođeni pretpostavkom da protein FADD (engl. Fas-Associated protein with Death Domain) sudjeluje u prijenosu apoptotskih, nekroptotskih i autofagnih signala nakon primjene NB-UVB (engl. Narrowband Ultraviolet B) zračenja, istražili smo njegovu ulogu smrtonosnog adaptera na modelu mišjih embrionalnih fibroblasta koji nemaju gen za protein FADD. Rezultati ovog istraživanja pokazuju da divlji tip mišjih embrionalnih fibroblasta umire apoptotskim smrtonosnim mehanizmom nakon izlaganja NB-UVB zračenju i to aktivacijom mitohondrijskog puta, ali bez aktivacije proteina p53. Stanice koje nemaju gen za protein FADD nakon izlaganja NB-UVB zračenju umiru programiranom nekrozom i autofagijom, uz aktivaciju kaspaza 3 i 9, ali bez aktivacije proteina p53, Bax i Bcl-2. Rezultati ukazuju da su protein FADD, ali i kinaza RIP1 (engl. Receptor-interacting serine/threonine-protein kinase 1) nužni za pokretanje apoptotskog smrtonosnog mehanizma, dok protein FADD nije nužan za aktivaciju autofagije koja se javlja zajedno s programiranom nekrozom nakon izlaganja stanica NB-UVB zračenju.

Abstract (english)

Based on the presumption that FADD protein (Fas-Associated protein with Death Domain) intermediates apoptotic, necroptotic and autophagic signals after exposure to NB-UVB (Narrowband Ultraviolet B) irradiation, we tested its role of death adaptor using FADD knockout mouse embrionic fibroblasts. The results show that wild type mouse embryonic fibroblast die by triggering apoptotic death signals through mitochondrial control, but independently of p53. FADD knockout mouse embrionic fibroblasts die by programmed necrosis and autophagy, by activating caspase-3 and -9. Their necrotic programme does not involve p53 nor Bax and Bcl-2. The results show that protein FADD, as well as RIPK1 (Receptor-interacting serine/threonine-protein kinase 1), are essential for triggering apoptotic cell death mechanism. FADD protein is not necessary for autophagic mechanism followed by necroptosis after NB-UVB irradiation.

• Keywords: protein FADD; apoptoza; nekroptoza; autofagija; programirana stanična smrt
• Keywords (english): FADD protein; apoptosis; necroptosis; autophagy; programmed cell death
• Language: croatian
• URN:NBN: urn:nbn:hr:217:573841
• Study programme: Title: Biology; Study programme type: university; Study level: postgraduate; Academic / professional title: doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija (doktor/doktorica znanosti, područje prirodnih znanosti, polje biologija)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-17 12:00:06