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Федеральное государственное бюджетное учреждение науки
Институт теоретической и экспериментальной биофизики
Российской академии наук


ООО "ИЦ КОМКОН"

ФГБУ НКЦТ им. С.Н. Голикова ФМБА России

Адрес редакции и реквизиты

192012, Санкт-Петербург, ул.Бабушкина, д.82 к.2, литера А, кв.378

Свидетельство о регистрации электронного периодического издания ЭЛ № ФС 77-37726 от 13.10.2009
Выдано - Роскомнадзор

ISSN 1999-6314


Фундаментальные исследования •

Том: 26
Статья: « 9 »
Страницы:. 211-256
Опубликована в журнале: 16 июня 2025 г.
English version

Роль цинка в регуляции белком A20 NF-κB-сигнального пути (Обзор литературы)

Лалетин В.С.

ФГБОУ ВО «Иркутский государственный медицинский университет» Минздрава России, 664003, Российская Федерация, г. Иркутск, ул. Красного восстания, д.1.
ФГБОУ ВО «Санкт-Петербургский государственный педиатрический медицинский университет» Минздрава России, 194100, Российская Федерация, г. Санкт-Петербург, ул. Литовская, д.2


Резюме
Цинк участвует в регуляции воспаления. Противовоспалительные эффекты цинка сопряжены с подавлением активности транскрипционного фактора NF-κB, одного из ключевых регуляторов воспаления. Активация NF-κB-сигнального пути сопровождается индукцией белка A20 (TNFAIP3), который является ключевым отрицательным регулятором NF-κB, действующим по механизму отрицательной обратной связи. Механизмы подавления активности NF-κB белком A20 обусловлены его убиквитин-редактируюшей функцией. Белок A20 является, вероятно, главной мишенью для ионов цинка в регуляции активности NF-κB-сигнального пути. Цинк участвует в функционировании A20 как структурный компонент, так и регулятор его экспрессии. В клинических исследованиях гаплонедостаточности A20 и в экспериментах на животных с направленными инактивирующими мутациями показано, что именно ZnF-домен белка A20, содержащий семь цинковых пальцев, играет ключевую роль в регуляции воспалительных процессов. В настоящее время механизмы индукции A20 цинком неизвестны. Исследования на различных линиях клеток и на животных продемонстрировали, что ионы цинка активируют экспрессию A20, действуя через цинк-чувствительные GPR39 рецепторы и эпигенетические механизмы регуляции. A20 вовлечен в патогенез хронических и острых воспалительных, аутоиммунных, сердечно-сосудистых и онкологических заболеваний. Роль цинка в регуляции и функционировании A20 и значение A20 в качестве терапевтической мишени позволяет определить направление дальнейших исследований терапевтического потенциала цинка в лечении широкого ряда заболеваний.


Ключевые слова
цинк; воспаление; противовоспалительное действие; провоспалительные цитокины; полиубиквитин; гаплонедостаточность A20; хронические воспалительные заболевания; аутоиммунные заболевания; сердечно-сосудистые заболевания; онкологические заболевания


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