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Mechanisms promoting and inhibiting the process of proteasomal degradation of cells

Abstract

Defects in the process of degradation of unneeded cellular proteins underlie many diseases. This article discusses one of the most important systems of removal of abnormal proteins. It describes the process of ubiquitination of proteins for proteasome degradation. It also describes the structure of the 26S and 20S proteasomes and the mechanism of ubiquitin-proteasome system. Proteasome proteolytic system is highly specialized and organized. Protease-proteasome 26S is particularly important for proper cell functioning. It recognizes and degrades marked proteins. Inhibition of proteasome pathway leads to cell cycle arrest and apoptosis.

Efficient degradation of cellular proteins by UPS (the ubiquitin - proteasome system) - is important for signal transduction, transcriptional regulation, response to stress and the activity control of cell receptors.

The development of many diseases has its origin in the dysfunction of the UPS route. This group includes diseases such as cancer, neurodegenerative disorders, immune-mediated diseases and infectious diseases. Development of effective methods for pharmacological intervention in the functioning of this system has become a great challenge. The use of specific, low molecular-weight proteasome inhibitors and enzymes catalyzing the ubiquitination gives hope for new, targeted therapies.

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An overlooked issue: sexual dysfunctions in men addicted to alcohol

, Poupon R. Hepatic uptake of sex steroids in men with alcoholic cirrhosis. Gastroenterology 1987; 92: 203–207. 54. Pajarinen JT, Karhunen PJ. Spermatogenic arrest and ‘Sertoli cell-only’ syndrome-common alcohol-induced disorders of the human testis. Int J Androl 1994; 17:292–299. 55. Morgan MY. Sex and alcohol. Br Med Bull 1982; 38:43-48. 56. Kozielewicz D, Dybowska D, Holota W. Wybrane aspekty kliniczne nadużywania alkoholu. Medical Science Review – Hepatologia 2011; 11:115-117. 57. Singleton CK, Martin PR. Molecular mechanisms of thiamine

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