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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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Jakub Chlebowski, Rector Magnificus Exultus – A Distinguished Professor of Internal Medicine in Postwar North-East Poland

Abstract

Jakub Chlebowski (Jakub Frydman) (1905-1969) was a distinguished professor of internal medicine and skillful organizer of health care system in Bialystok region in the North east Poland. He graduated medicine in 1929 and worked at local university in prewar Vilnius. During World War Two, arrested by the Soviets and exiled to Siberian work camps he managed to return to Poland with Kosciuszko Division of Polish Army. Then, he continued to serve as a military and university medical doctor in Cracow and Lodz, finally to take over position of director of Internal Diseases Department in 1951 in Bialystok, holding an office of rector magnificus of Medical University of Bialystok from 1959 to 1962. Chlebowski trained generations of internal medicine specialists, who later became eminent representatives of emerging branches of internal medicine as distinct subspecialties in the field of cardiology, endocrinology and gastroenterology in Bialystok. In course of anti-Semitic campaign during March Events in 1968, he was disposed from the post of director of the university hospital department. Constantly harassed, he immigrated with the family to Israel to die in public traffic accident in 1969. Jakub Frydman, who survived not only hunger of food, but also metaphorical “hunger of humanity” during World War Two, turned out to be as good and useful as daily bread for Polish community after wartime. He was so devoted in this action, that he even changed his surname into Chlebowski (Polish: Chleb=English: Bread). In this way, due to similar experience and experience-shaped mentality, Chlebowski could be counted among medical authorities of the time, the individuals with such a high moral standard as Janusz Korczak (1878 or 1879-1942) or Julian Kramsztyk (1851-1926).

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in PRILOZI
Biventricular Hypertrophic Cardiomyopathy in a Child with LEOPARD Syndrome: a Case Report

heart disease as life-threatening conditions in the Emergency Room. Journal of Cardiovascular Emergencies . 2016;2:7-10. 12. Woywodt A, Welzel J, Haase H, et al. Cardiomyopathic Lentiginosis/LEOPARD Syndrome presenting as sudden cardiac arrest. Chest . 1998;113:1415-1417.

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Variations of sphenoid pneumatization: a CBCT study

transsphenoidal approach to pituitary adenoma. Minimally Invasive Neurosurgery: MIN, 2011;54:162-166. 22. Stuehmer C., Essig H., Bormann K.H., Majdani O., Gellrich N.C., Rucker M. - Cone beam CT imaging of airgun injuries to the craniomaxillofacial region. Int J Oral Maxillofac Surg., 2008;37:903-906. 23. Jalali E., Tadinada A. - Arrested pneumatization of the sphenoid sinus mimicking intraosseous lesions of the skull base. Imaging Science in Dentistry, 2015;45:67-72.

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Procedural Sedation and Analgesia in Adults - new trends in patients safety

, Galli SJ The pathophysiology of anaphylaxis. Journal of Allergy and Clinical Immunology. 2017; 140(2):335-348. 37. Goudra B, Nuzat A, Singh PM, et al. Car­diac arrests in patients undergoing gastro­intestinal endoscopy: A retrospective anal­ysis of 73,029 procedures. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 2015; 21(6):400-11. 38. Crosby G, Culley DJ, & Marcantonio ER. Delirium: a cognitive cost of the comfort of procedural sedation in elderly patients?. Mayo Clinic proceedings. 2010

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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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Procedural Sedation and Analgesia in Adults - new trends in patients safety

. Reber LL, Hernandez JD, Galli SJ The pathophysiology of anaphylaxis. Journal of Allergy and Clinical Immunology. 2017; 140(2):335-348. 37. Goudra B, Nuzat A, Singh PM, et al. Cardiac arrests in patients undergoing gastrointestinal endoscopy: A retrospective analysis of 73,029 procedures. Saudi journal of gastroenterology: official journal of the Saudi Gastroenterology Association. 2015; 21(6):400-11. 38. Crosby G, Culley DJ, & Marcantonio ER. Delirium: a cognitive cost of the comfort of procedural sedation in elderly patients?. Mayo Clinic proceedings

Open access