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Context-dependent roles of cyclin-dependent kinase inhibitors (CDKi) in cancer
Doležalová, Šárka ; Janoštiak, Radoslav (advisor) ; Macůrek, Libor (referee)
Cell cycle progression is intricately regulated by many proteins. Among these proteins, cyclin- dependent kinase inhibitors (CKIs) play a key role, traditionally associated with cyclin- dependent kinase (CDK) inhibition and cell cycle arrest. However, recent research reveals that their function is much more complex in the context of cancer. CKI inhibitors are not mutated at all in many tumor types, and their expression is maintained or even increased, suggesting additional mechanisms by which they influence tumor pathogenesis. Post-translational modifications, especially phosphorylation, which affect their localization and stability, have a fundamental influence on their function. These modifications can then, for example, affect cell motility, apoptosis, or DNA repair. This can convert CKIs from tumor suppressors to tumor promoters or vice versa, strengthening their tumor suppressor properties. Key words: Cyclin-dependent kinases, inhibitors of cyclin-dependent kinases, cell cycle, cancer, post-translational modification
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Role of Zinc-α2-glycoprotein in tumors
Kotvalová, Hanka ; Šmahel, Michal (advisor) ; Kubů, Martin (referee)
The Zinc-α2-glycoprotein (ZAG) encoded by the AZGP1 gene particularly contributes to the regulation of lipid and glucose metabolism. In different types of tumors, its altered production was found and the association of the ZAG level with the patient's prognosis was suggested. However, the role of ZAG in tumor progression can differ in individual malignancy types and mechanisms of ZAG function are not sufficiently identified. The objectives of the bachelor's thesis are a description of the structure of the ZAG protein and the regulation of AZGP1 expression, a summary of the identified ZAG functions in nonmalignant diseases, and a focus on the role of ZAG in tumors, particularly on the mechanisms of its action and its potential use as a biomarker.
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