prikaz prve stranice dokumenta Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations
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master's thesis
Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations
Zagreb: University of Zagreb, School of Medicine, 2018. urn:nbn:hr:105:244521
Wilson, Damien Jonas Adolphus
University of Zagreb
School of Medicine
Department of Medical Biology

Institutional repository: Dr Med - University of Zagreb School of Medicine Digital Repository

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Wilson, D. J. A. (2018). Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations (Master's thesis). Zagreb: University of Zagreb, School of Medicine. Retrieved from https://urn.nsk.hr/urn:nbn:hr:105:244521

Wilson, Damien Jonas Adolphus. "Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations." Master's thesis, University of Zagreb, School of Medicine, 2018. https://urn.nsk.hr/urn:nbn:hr:105:244521

Wilson, Damien Jonas Adolphus. "Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations." Master's thesis, University of Zagreb, School of Medicine, 2018. https://urn.nsk.hr/urn:nbn:hr:105:244521

Wilson, D. J. A. (2018). 'Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations', Master's thesis, University of Zagreb, School of Medicine, accessed 27 August 2024, https://urn.nsk.hr/urn:nbn:hr:105:244521

Wilson DJA. Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations [Master's thesis]. Zagreb: University of Zagreb, School of Medicine; 2018 [cited 2024 August 27] Available at: https://urn.nsk.hr/urn:nbn:hr:105:244521

D. J. A. Wilson, "Human folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations", Master's thesis, University of Zagreb, School of Medicine, Zagreb, 2018. Available at: https://urn.nsk.hr/urn:nbn:hr:105:244521

Metadata
TitleHuman folliculin delays cell cycle progression through late S and G2/M-phases: effect of phosphorylation and tumor associated mutations
Title (croatian)Ljudski folikulin odgađa napredovanje staničnog ciklusa putem kasne S i G2/M faze: učinak fosforilacije i mutacija povezanih s tumorom
AuthorDamien Jonas Adolphus Wilson
MentorMaja Vlahović (mentor)
Committee memberFloriana Jakuš (predsjednik povjerenstva)
Committee memberLjiljana Šerman (član povjerenstva)
Committee memberMaja Vlahović (član povjerenstva)
GranterUniversity of Zagreb
School of Medicine
(Department of Medical Biology)
Zagreb
Defense date and country2018-07-13, Croatia
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Medical Microbiology
Abstract
The Birt-Hogg-Dube disease occurs as a result of germline mutations in the human Folliculin gene (FLCN), and is characterized by clinical features including fibrofolliculomas, lung cysts and multifocal renal neoplasia. Clinical and genetic evidence suggest that FLCN acts as a tumor suppressor gene. The human cell line UOK257, derived from the renal cell carcinoma of a patient with a germline mutation in the FLCN gene, harbors a truncated version of the FLCN protein. Reconstitution of the wild type FLCN protein into UOK257 cells delays cell cycle progression, due to a slower progression through the late S and G2/M-phases. Similarly, Flcn–/– mouse embryonic fibroblasts progress more rapidly through the cell cycle than wild type controls (Flcnflox/flox). The reintroduction of tumor-associated FLCN mutants (FLCN DF157, FLCN 1–469 or FLCN K508R) fails to delay cell cycle progression in UOK257 cells. Additionally, FLCN phosphorylation (on Serines 62 and 73) fluctuates throughout the cell cycle and peaks during the G2/M phase in cells treated with nocodazole. In keeping with this observation, the reintroduction of a FLCN phosphomimetic mutant into the UOK257 cell line results in faster progression through the cell cycle compared to those expressing the wild type FLCN protein. These findings suggest that the tumor suppression function of FLCN may be linked to its impact on the cell cycle and that FLCN phosphorylation is important for this activity. Additionally, these observations describe a novel in vitro assay for testing the functional significance of FLCN mutations and/or genetic polymorphisms.
Abstract (croatian)
Birt-Hogg-Dubeova bolest razvija se kao rezultat zametnih mutacija u ljudskom genu za folikulin (FLCN), a karakteriziraju je kliničke promjene poput razvoja fibrofolikuloma, plućnih cisti i multifokalne neoplazije bubrega. Dosadašnji klinički i genetički dokazi ukazuju na to da FLCN djeluje kao tumor-supresorski gen. Ljudska stanična kultura UOK257, dobivena od pacijenta s karcinomom bubrežnih stanica s pratećom zametnom mutacijom gena FLCN, specifična je zbog postojanja skraćene verzije bjelančevine FLCN. Rekonstitucija divljeg tipa bjelančevine FLCN u UOK257 stanice odgađa napredovanje staničnog ciklusa kroz kasnu S i G2/M fazu. Na sličan način Flcn-/- mišji embrijski fibroblasti napreduju znatno brže kroz stanični ciklus u usporedbi s kontrolnim divljim tipovima (Flcnflox/flox). Reintrodukcija mutiranih oblika gena FLCN (FLCN ΔF157, FLCN 1-469 or FLCN K508R) ne uspjeva odgoditi napredovanje staničnog ciklusa u UOK257 stanicama. Nadalje, fosforilacija FLCN-a (na serinu 62 i 73) fluktuira tijekom staničnog ciklusa, a vršnu vrijednost postiže tijekom G2/M faze u stanicama tretiranim nokodazolom. U skladu s navedenim opažanjem, ponovni unos fosfomimetičkog FLCN mutanta u UOK257 stanice rezultira bržim napredovanjem kroz stanični ciklus u usporedbi sa staničnom linijom koja nosi divlji tip bjelančevine FLCN. Ovi rezultati ukazuju na to da bi tumor-supresorska funkcija FLCN-a mogla biti povezana s njegovim učinkom na stanični ciklus, ali i da je fosforilacija FLCN-a jedan od ključnih koraka za tu aktivnost. Osim toga, ova zapažanja opisuju sasvim novi in vitro model za testiranje funkcionalne značajnosti mutacija gena FLCN i/ili genetskih polimorfizama.
Keywords
Keywords (croatian)
Languageenglish
URN:NBNurn:nbn:hr:105:244521
Study programmeTitle: Medicine (in English language)
Study programme type: university
Study level: integrated undergraduate and graduate
Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2019-04-26 12:16:01