Razgradnja pogrešno smotanih modelnih proteina tGnd1, stGnd1 i NBD2* u kvascu Saccharomyces cerevisiae na podlozi siromašnoj glukozom

master's thesis

• Title (english): Degradation of model misfolded proteins tGnd1, stGnd1 and NBD2* in glucose-starved yeast Saccharomyces cerevisiae
• Author: Dominik Guzalić
• Mentor: Mirta Boban (mentor)
• Mentor: Inga Urlić (komentor)
• Committee member: Inga Urlić (predsjednik povjerenstva)
• Committee member: Sandra Hudina (član povjerenstva)
• Committee member: Maja Matulić (član povjerenstva)
• Committee member: Sunčica Bosak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2023-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Homeostaza proteina ključna je za funkcioniranje svih staničnih procesa. Jedan od osnovnih načina
održanja homeostaze proteina je razgradnja proteina sustavom ubikvitin-proteasoma, te procesom
autofagije. Dosad provedena istraživanja na stanicama kvasca Saccharomyes cervisiae uzgajanim
na mediju bogatom glukozom pokazala su da se modelni pogrešno smotani proteini NBD2*, tGnd1
i stGnd1 razgrađuju selektivno sustavom ubikvitin-proteasoma. Cilj ovog rada bio je ispitati dolazi
li u stanicama kvasca u uvjetima akutnog uskraćivanja glukoze do selektivne razgradnje pogrešno
smotanog modelnog proteina NBD2*. Osim toga, budući da je poznato kako gladovanje inducira
autofagiju, drugi cilj bio je ispitati je li za razgradnju pogrešno smotanih proteina tGnd1 i stGnd1
odgovorna autofagija. Rezultati su pokazali da se modelni pogrešno smotani protein NBD2* u
uvjetima akutnog uskraćivanja glukoze razgrađuje selektivno. Nadalje, rezultati pokazuju kako se
pogrešno smotani protein stGnd1 razgrađuje molekulskim putem neovisnim o autofagiji, za razliku
od pogrešno smotanog proteina tGnd1 koji se u navedenim uvjetima razgrađivao autofagijom.
Dobiveni rezultati pokazuju kako je moguće da se različiti pogrešno smotani proteini u uvjetima
akutnog uskraćivanja glukoze u stanicama kvasca razgrađuju različitim molekulskim putevima.

Abstract (english)

Protein homeostasis is crucial for the functioning of all cellular processes. One of the fundamental
mechanisms for maintaining protein homeostasis is protein degradation through the ubiquitinproteasome system and the process of autophagy. Previous research conducted on Saccharomyces
cerevisiae yeast cells cultured in glucose-rich media has shown that the model misfolded proteins
NBD2*, tGnd1, and stGnd1 are selectively degraded by the ubiquitin-proteasome system. The aim
of this study was to investigate whether selective degradation of the model misfolded protein
NBD2* occurs in yeast cells under conditions of acute glucose deprivation. Additionally, since it
is known that starvation induces autophagy, another goal was to examine whether autophagy is
responsible for the degradation of misfolded proteins tGnd1 and stGnd1. The results demonstrated
that the model misfolded protein NBD2* is selectively degraded under conditions of acute glucose
deprivation. Furthermore, the results indicate that the misfolded protein stGnd1 is degraded
through a molecular pathway independent of autophagy, in contrast to the misfolded protein tGnd1
which was degraded by autophagy under the mentioned conditions. The obtained results suggest
that different misfolded proteins may be degraded through distinct molecular pathways in yeast
cells during acute glucose deprivation.

• Keywords: sustav ubikvitin-proteasom; autofagija; proteostaza; cikloheksimid
• Keywords (english): Ubiquitin-proteasome system; autophagy; proteostasis; cycloheximide
• Language: croatian
• URN:NBN: urn:nbn:hr:217:328937
• Project: Number: PZS-2019-02-3610; Title: Kontrola kvalitete proteina putem selektivne razgradnje u stanicama u mirovanju; Title: Degradation-mediated protein quality control in quiescent cells; Acronym: Q-CTRL; Leader: Mirta Boban; Jurisdiction: Croatia; Funder: HRZZ; Funding stream: Nema
• Project: Number: KK.01.1.1.01.0007; Title: Eksperimentalna i klinička istraživanja hipoksijsko-ishemijskog oštećenja mozga u perinatalnoj i odrasloj dobi; Leader: Ivica Kostović; Jurisdiction: Croatia; Funder: EK
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Embargoed access; Embargo expiration date: 2025-09-27
• Created on: 2023-10-17 11:04:39