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Molecular requirements of LACTB-induced tumor suppression
Jakoubě, Pavel ; Kečkéšová, Zuzana (advisor) ; Rohlenová, Kateřina (referee)
LACTB is a recently discovered mitochondrial tumour suppressor protein operating in many different types of tissues. Its mechanism-of-action seems to be context dependent as it has been shown to suppress carcinogenesis through the induction of cell cycle arrest, apoptosis, differentiation and suppression of EMT. These processes can be further dependent on alterations of lipid metabolism and interactions with additional tumour suppressors and signalling pathways. LACTB is derived from bacterial penicillin binding proteins, is localized to the mitochondrial intermembrane space and possesses enzymatic activity. It was shown to form filaments, which consist of two intertwined antiparallel chains, suggesting its role in the organisation of mitochondrial intermembrane space. In the first aim of my thesis, I wanted to examine in more detail the molecular requirement for LACTB's filament formation with the specific focus on the role of disulphide bonds in this process. In the second aim of my thesis, I intended to uncover the binding partners of LACTB, which might have a role in the filament formation. Realizing both aims will uncover important requirements for the proper folding and biological activity of LACTB. Key words: LACTB, tumour suppressor, cancer, structure, disulphide bonds, protein interactions
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Mitochondrial tumour suppressors
Jakoubě, Pavel ; Kečkéšová, Zuzana (advisor) ; Černý, Jan (referee)
Cancer is one of the most feared diseases in our modern society and many resources are spent on developing new ways of diagnosis, prevention and treatment. Luckily for us, our bodies already have a first line of defence against carcinogenesis - proteins called tumour suppressors. Studying these proteins can give us an important insight into the inner workings of this disease and can also show us new ways of combating it. One of the signs of cancer cells is dysregulation of metabolic processes and since mitochondria play a pivotal part in many of these processes, we wanted to research the identity and role of mitochondrial tumour suppressors. Indeed, several such tumour suppressors have been identified, having a plethora of functions such as modulating the activity of other mitochondrial enzymes, directly participating in cellular metabolic pathways, affecting reactive oxygen species production and modulating hypoxia-induced signalling. The focus of this work is to gather the available information about these important protective proteins. Key words: cancer, tumour suppressor, SIRT3, SIRT4, POX/PRODH, MTUS1/MTSG1, FUS1/TUSC2, LACTB, FH, SDH, mitochondrial
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