Medical academic journalMedical academic journalМедицинский академический журнал1608-41012687-1378Eco-Vector7962310.17816/MAJ79623Analytical reviewsАналитические обзорыReview ArticleMultiple functions of tumor supressor p53Множественные функции опухолевого супрессора p53https://orcid.org/0000-0003-0156-88217246-7349GudkovaAlexandra Ya.ГудковаАлександра Яковлевна
Russian Federation

MD, Dr. Sci. (Med.), Head of the Laboratory of Cardiomyopathies of Heart and Vascular Research Institute, Professor of the Department of Faculty Therapy; Leading Researcher of the Institute of Molecular Biology and Genetics

д-р мед. наук, заведующая лабораторией кардиомиопатий НИИ сердечно-сосудистых заболеваний НКИЦ, профессор кафедры факультетской терапии; ведущий научный сотрудник Института молекулярной биологии и генетики

alexagood-1954@mail.ruhttps://orcid.org/0000-0003-2843-7688360197916009214-2677AntimonovaOlga I.АнтимоноваОльга Игоревна
Russian Federation

Junior Researcher of the Department of Molecular Genetics

младший научный сотрудник Отдела молекулярной генетики

oa0584@mail.ruhttps://orcid.org/0000-0002-2119-476XE-4115-20145009-9383ShavlovskyMikhail M.ШавловскийМихаил Михайлович
Russian Federation

MD, Dr. Sci. (Med.), Professor, Head of the Laboratory of Human Molecular Genetics of the Department of Molecular Genetic; Leading Researcher of the Laboratory of Cardiomyopathies of Heart and Vascular Research Institute

д-р мед. наук, профессор, заведующий лабораторией молекулярной генетики человека Отдела молекулярной генетики; ведущий научный сотрудник лаборатории кардиомиопатий НИИ сердечно-сосудистых заболеваний НКИЦ

mmsch@rambler.ruPavlov First Saint Petersburg State Medical UniversityПервый Санкт-Петербургский государственный медицинский университет имени академика И.П. ПавловаAlmazov National Medical Research CentreНациональный медицинский исследовательский центр имени В.А. АлмазоваInstitute of Experimental MedicineИнститут экспериментальной медицины180420221907202222173881609202118042022Copyright ©; 2022, Gudkova A.Y., Antimonova O.I., Shavlovsky M.M.Copyright ©; 2022, Гудкова А.Я., Антимонова О.И., Шавловский М.М.2022Gudkova A.Y., Antimonova O.I., Shavlovsky M.M.Гудкова А.Я., Антимонова О.И., Шавловский М.М.https://creativecommons.org/licenses/by-nc-nd/4.0https://journals.eco-vector.com/MAJ/article/view/79623

One of the most investigated and inscrutable eukaryotic proteins is a factor positioned as tumor suppressor which structural changes are observed in 50% of malignant cells. In the literature this protein is referred to as p53. The generalized function of p53 resolves to maintaining of cell genetic stability and preventing cell automatization. Therefore, p53 was called the “keeper”, or “guardian”, of the genome. Suppressive activity of p53 in regard to appearance of malignant cells seems to be side function of this protein. The present review prоvides data on the role of p53 in various vital processes in eukaryotic cells. p53 is a complex protein in its domain structure, and the semi-autonomous role of individual domains is clearly discernible. Normally, p53 is not a crucial factor in ontogenesis. At the same time p53 modulates the activity of about 500 different genes and also maintains homeostasis in cells and organism directly via protein-protein interactions. In response to exogenous and endogenous impacts p53 provides a balance of cellular metabolism and either promotes elimination of abnormalities, or triggers an apoptotic cascade. The review summarizes current considerations of p53 multiple functions as well as discusses already established and not yet disclosed mechanisms concerning involvement of said factor in cellular metabolism.

Один из наиболее изучаемых и загадочных белков эукариотических организмов — фактор, позиционируемый как опухолевый супрессор, структурные изменения которого наблюдаются в 50 % злокачественных клеток. Этот белок в литературе обозначают как p53. Обобщенная функция p53 сводится к сохранению генетической стабильности клеток и предотвращению их автономизации, поэтому p53 получил название «хранитель» или «страж» генома. Супрессорная активность p53 в отношении возникновения злокачественных клеток, по-видимому, является побочной функцией данного белка. В настоящем обзоре представлены данные о роли p53 в различных процессах жизнеобеспечения эукариотических клеток. p53 — сложный с точки зрения доменной структуры белок, в котором отчетливо прослеживается полуавтономная роль отдельных доменов. В норме p53 не является критически важным фактором онтогенеза, в то же время модулирует активность около 500 различных генов, а также непосредственно за счет белок-белковых взаимодействий поддерживает гомеостаз в клетках и организме. В ответ на экзогенные и эндогенные воздействия p53 обеспечивает баланс клеточного метаболизма и либо способствует устранению нарушений, либо запускает апоптотическй каскад. В обзоре суммированы современные представления о множественных функциях p53, а также обсуждены уже установленные и еще не раскрытые механизмы участия этого фактора в клеточном метаболизме.

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