IBMPFD GENETIC DISEASE-ASSOCIATED VCP MUTATIONS AND AUTOPHAGY
Biological Sciences and Bioengineering, Master Thesis, 2012
Assoc. Prof. Devrim Gözüaçık (Thesis Supervisor), Prof. Dr. Hikmet Budak, Prof. O.Uğur Sezerman, Asst. Prof. Bahattin Koç, Assoc. Prof. Ali Koşar
Date &Time: August 1st, 2012 – 13:00
Place: FENS G029
Key Words: Autophagy, ERAD, IBMPFD, VCP
VCP (p97) is a protein involved in many distinct cellular activities such as transcriptional regulation, membrane fusion, B and T cell activation, cell cycle regulation. It also plays a crucial role in the proteasome-dependent degradation of misfolded proteins. Mutations of VCP is the cause of an autosomal dominant genetic disease called IBMPFD. The disease is characterized by inclusion bodies in muscles, early-onset Paget’s disease of bone and frontotemporal dementia. Therefore, the condition affects muscles, bones, and the brain. IBMPFD is a fatal disease and currently there is no cure.
In this thesis, to better understand abnormalities causing the disease and its sypmtoms, effects of IBMPFD-associated mutants of the VCP protein were analyzed at a cellular and molecular level. Original and important findings related to the role of autophagy in disease progression were obtained. Our discoveries might pave the way for the development of novel treatment approaches against this incurable disease.