Молекулярная биология, 2022, T. 56, № 1, стр. 55-68

Мутагенная активность дезаминаз AID/APOBEC в противовирусной защите и канцерогенезе

О. Н. Шилова a, Д. Л. Цыба bc, Е. С. Шилов d*

a Институт биоорганической химии им. академиков М.М. Шемякина и Ю.А. Овчинникова Российской академии наук
117997 Москва, Россия

b Первый Санкт-Петербургский государственный медицинский университет им. акад. И.П. Павлова
197022 Санкт-Петербург, Россия

c Научно-технологический университет “Сириус”
354340 Сочи, Россия

d Биологический факультет Московского государственного университета им. М.В. Ломоносова
119234 Москва, Россия

* E-mail: shilov_evgeny@inbox.ru

Поступила в редакцию 28.12.2020
После доработки 23.04.2021
Принята к публикации 01.06.2021

Аннотация

Белки семейства AID/APOBEC способны дезаминировать цитидин в составе нуклеиновых кислот с образованием урацила. Эти ферменты используются клеткой для редактирования матричных РНК, защиты от вирусов, внесения точечных мутаций в ДНК в процессе соматического гипермутагенеза и переключения изотипов антител. Дезаминазы мощные мутагены, поэтому регуляция их экспрессии, активности и специфичности происходит сразу по нескольким механизмам, что особенно характерно для AID ‒ дезаминазы, способной перестраивать ядерный геном. В обзоре обсуждаются механизмы нарушения экспрессии и активации белков AID/APOBEC в опухолях человека, их роль в канцерогенезе и прогрессии опухолей. Также проанализировано диагностическое и потенциальное терапевтическое значение повышенной экспрессии AID/APOBEC в разных типах опухолей. Мы предполагаем, что в случае сóлидных опухолей повышенная экспрессия эндогенных дезаминаз может служить одним из маркеров ответа на иммунотерапию, так как множественные точечные мутации в ДНК хозяина приводят к аминокислотным заменам в последовательностях опухолевых белков и тем самым увеличивают вероятность возникновения неоэпитопов.

Ключевые слова: AID, APOBEC, мутагенез, опухоль, редактирование РНК, геномная нестабильность

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