БИОХИМИЯ, 2018, том 83, вып. 11, с. 1595–1605

УДК 576.358.3;577.218

Роль ковалентных модификаций в регуляции гена-супрессора опухолевого роста CDKN2A и кодируемого им белка p16-INK4a

Обзор

© 2018 Y. Jiao 1, Y. Feng 2, X. Wang 3*

School of physical education, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, P. R. China

Key Laboratory of Molecular Epigenetics of the Ministry of Education (MOE), Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, P. R. China

Central Laboratory of General Biology, School of Life Sciences, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin, 130024, P. R. China; E-mail: wangxl034@nenu.edu.cn

Поступила в редакцию 29.01.2018
После доработки 11.06.2018

DOI: 10.1134/S0320972518110015

КЛЮЧЕВЫЕ СЛОВА: p16-INK4a, модификация, метилирование, фосфорилирование; ацетилирование.

Аннотация

Ген CDKN2A является одним из наиболее известных регуляторов, участвующих в подавлении опухолевого роста. Он кодирует белок p16-INK4a, который играет важную роль в клеточном цикле, дифференциации клеток, их старении и апоптозе. Мутации гена CDKN2A человека или нарушение его функционирования часто связаны с различными видами рака. Являясь ингибитором циклинзависимых киназ (cyclin-dependent kinases 4/6, CDK4/6), p16-INK4a конкурирует с циклином D при образовании с ними комплекса. Принято считать, что для образования комплекса p16-CDK4 необходимы структуры типа «спираль–поворот–спираль», входящие в состав тандемно расположенных анкириновых повторов в белке p16-INK4a. До настоящего времени рассматривались отдельные механизмы, такие как мутации последовательности ДНК, гомозиготная или гетерозиготная потеря гена и метилирование промоторного участка гена CDKN2A, которые могут участвовать в контроле функций p16-INK4a, а также в развитии рака. В настоящем обзоре обсуждены недавно полученные результаты, которые позволяют дополнить наши представления о механизмах регуляции функционирования белка p16-INK4a, заключающихся в его ковалентной модификации, как на уровне транскрипции, так и на посттранскрипционном уровне.

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Финансирование

Работа выполнена при поддержке Национального фонда естественных наук Китая (National Natural Science Foundation of China, гранты № 31271442 и 31600645).

Благодарности

Авторы благодарны Baiqu Huang и Jun Lu за критические замечания и полезные советы. Мы также признательны за содействие Central Laboratory, School of Life Sciences, Northeast Normal University.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

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