Protutumorski lijekovi - inhibitori histonske deacetilaze kao epigenetički regulatori u procesu razvoja tumora

undergraduate thesis

• Title (english): Antitumor drugs - histone deacetylase inhibitors as epigenetic regulators in the process of tumor development
• Author: Laura Colar Zanjko
• Mentor: Blaženka Kos (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Antibiotic, Enzyme, Probiotic and Starter Cultures Technology); Zagreb
• Defense date and country: 2021-09-16, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Epigenetičke modifikacije, uključujući acetilaciju, metilaciju, fosforilaciju i ubikvitinaciju, igraju ključnu ulogu u regulaciji ekspresije gena. Među enzimima uključenim u epigenetičke modifikacije, histonska deacetilaza (HDAC) potiče relaksaciju kromatina te transkripciju gena. Nekoliko HDAC izoenzima je prekomjerno eksprimirano u različitim malignim bolestima i njihova inhibicija je pristup koji se koristi u razvoju novih protutumorskih lijekova. Na temelju toga provode se klinička istraživanja inhibitora HDAC te su do sada četiri lijeka odobrena od FDA (vorinostat, romidepsin, belinostat i panobinostat). Dokazano je da inhibitori HDAC izazivaju pogrešno savijanje i agregaciju proteina, no mehanizmi njihovog djelovanja nisu u potpunosti istraženi. Pretpostavlja se da mijenjaju način acetilacije citoplazmatskih proteina, što pridonosi njihovom protutumorskom potencijalu. Nedavna istraživanja su dokazala da su sustavi kontrole kvalitete proteina uključeni u prepoznavanje modificiranog načina acetilacije nakon liječenja s inhibitorima HDAC.

Abstract (english)

Epigenetic modifications, including acetylation, methylation, phosphorylation, and ubiquitination, play a key role in regulating gene expression. Among the enzymes involved in epigenetic modifications, histone deacetylase (HDAC) promotes chromatin relaxation and gene transcription. Several HDAC isoenzymes are overexpressed in various malignancies and their inhibition is an approach used in the development of new antitumor drugs. Based on this, clinical trials of HDAC inhibitors are being conducted and so far four drugs have been approved by the FDA (vorinostat, romidepsin, belinostat and panobinostat). HDAC inhibitors have been shown to cause protein misfolding and aggregation, but their mechanisms of action have not been fully investigated. They are thought to alter the way acetylation of cytoplasmic proteins occurs, contributing to their antitumor potential. Recent research has shown that protein quality control systems are involved in recognizing a modified mode of acetylation after treatment with HDAC inhibitors.

• Keywords: acetilacija; epigenetički regulatori; inhibitori histonske deacetilaze; protutumorsko djelovanje
• Keywords (english): acetylation; antitumor activity; epigenetic regulators; histone deacetylase inhibitors
• Language: croatian
• URN:NBN: urn:nbn:hr:159:668382
• Study programme: Title: Biotechnology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka biotehnologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) inženjer/inženjerka biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-09-29 09:24:14