Regulacija staničnog ciklusa ubikvitinacijom proteina

undergraduate thesis

• Title (english): Cell cycle regulation by protein ubiquitination
• Author: Marija Klasić
• Mentor: Dunja Leljak-Levanić (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2009, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Stanični ciklus eukariotskih stanica mora biti vrlo precizno reguliran. Prilikom stanične diobe događaju se morfološke promjene koje su prostorno i vremenski dobro regulirane tako da bi se genom jednako raspodijelio u stanice kćeri. Regulacija se postiže fosforilacijom proteina i ciljanom razgradnjom. Razgradnja je ovisna o ubikvitinu, a u cijelom procesu sudjeluju 3 tipa enzima: E1, enzim koji aktivira ubikvitin, E2, enzim koji spaja ubikvitin i E3, ubikvitin protein ligaza. Najvažnije vrste E3 ubikvitin ligaza koje sudjeluju u regulaciji staničnog ciklusa su ligaze tipa APC/C, SCF i E3 ligaze ovisne o kulinu3. Ligaze APC/C omogućuju prijelaz iz metafaze u anafazu degradiranjem sekurina koji je inhibitor separaze i izlazak iz mitoze degradiranjem mitotskih ciklina. SCF-kompleksi reguliraju rane stadije mitoze i citokinezu. Oni sudjeluju u kontroli aktivnosti kompleksa Cdc2-ciklin B, jednog od ključnih regulatora staničnog ciklusa. Njegovom aktivacijom potiče se prijelaz iz G2- u M-fazu. Ligaze ovisne o kulinu3 kontroliraju položaj kromosoma i citokinezu. Kod ljudi je kompleks kulin3-KLHL9-KLHL-13 potreban za pravilno vezanje kromosoma i napredovanje mitoze tako što ubikvitinira protein Aurora B koji disocira s mitotskih kromosoma prilikom njihovog poravnavanja u metafaznu ploču. Da bi došlo do razdvajanja sestrinskih kromatida u anafazi, mora se degradirati kohezin koji ih drži zajedno. Za izlazak iz mitoze važna je inaktivacija kinaza ovisnih o ciklinima (CDK). U regulaciji staničnog ciklusa sudjeluje puno proteina koji su indirektno ili direktno povezani. U cijeloj toj mreži proteina, vrlo je teško otkriti sve proteine i njihove funkcije koje su vjerojatno mnogobrojne.

Abstract (english)

Cell cycle of eukaryotic cells has to be strictly regulated. During cell division, many morphological changes which are temporary and spatially precisely regulated occur to ensure equal distribution of the newly replicated copies of genome into the two daughter cells. Two mechanisms ensure cell cycle regulation: phosphorylation and targeted proteolysis. Targeted, ubiquitin-dependent proteolysis is regulated by three types of enzymes: E1, ubiquitin-activating enzyme, E2, ubiquitin-conjugating enzyme and E3, ubiquitin protein ligase. Most important E3 ligases which regulate cell cycle are APC/C, SCF and Cullin3-based E3 ligase complex. The APC/C is required for triggering the metaphase to anaphase transition and mitotic exit regulation. This complex degrades the separase inhibitor securin and mitotic cyclins. SCF complexes regulate early stages of mitosis and citokinesis by the control of Cdc2-cyclin B activity, a key regulator of cell cycle. It ensures G2 to M phase transition. Cullin3-based E3 ligases control chromosome position and citokinesis. Human Cullin3- KLHL9-KLHL-13 complex ensures chromosome attachment and progress of mitotis by degradation of Aurora B which dissociate from mitotic chromosome during chromosome alignment in prometaphase. Sister chromatids are held together by cohesin, which has to be eliminated for proper chromosome segregation in anaphase. Cyclin-dependend kinases (CDKs) inactivation is very important for mitotic exit. Many proteins, which are directly or indirectly connected, are involved in cell cycle regulation. In this network, it is very difficult to find out every single protein and its functions.

• Keywords: stanični ciklus; ubikvitinacija proteina
• Keywords (english): cell cycle; protein ubiquitination
• Language: croatian
• URN:NBN: urn:nbn:hr:217:428700
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2018-03-12 13:01:16