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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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