Ubiquitin-26s proteasome system. New therapeutic implications (review)

The article reviews Ubiquitin-26S proteasome system (UPS), which is an ATP-dependent protein degradation mechanism in eukaryotic cells. UPS effects many principal substrates and cellular processes, therefore, it is not surprising that aberrations in the system may be implicated in pathogenesis of many diseases. Alterations in the UPS are correlated with a variety of human pathologies, like cancer, immunological disorders, inflammation, neurodegenerative, liver diseases and etc. It is believed that ubiquitin cascade components E1, E2, E3, ubiquitin, proteasome, substrate protein, are useful in discover of new therapeutic possibilities. All kinds of aberrations have been found in ubiquitin-26S proteasome system, among them: truncated version of ubiquitin (Acute Lymphoblastic Leukaemia), elongated ubiquitin (Alcoholic Liver Disease), suppressed proteasome, accelerative degradation, decreased rates of degradation and etc. As irreversible course of cell cycle is very sensitive to protein degradation process, each of these derangements may cause proliferative disorders and hence development of heavy diseases. It is too difficult to identify a narrow window between benefits and toxicity of drugs used in treatment of different diseases. That is why is so important to discover inhibitors or activators of intracellular mechanisms for protein degradation due to development of targeted therapy.