Рецептор глюкокортикоидов: переход из цитоплазмы в клеточное ядро, хроматиновый и внутриядерный шапероновый циклы

Рецептор глюкокортикоидных гормонов (ГР) является лигандзависимым фактором транскрипции, регулирующим экспрессию сотен генов. В отсутствие гормона ГР находится в цитоплазме клетки в комплексе c молекулярными шаперонами hsp90, hsp70, p23, Hop, FKBP51, FKBP52 и др. В составе этого комплекса ГР приобретает конформацию, обладающую высоким сродством к глюкокортикоидам. После связывания с гормоном рецептор высвобождается из комплекса с шаперонами и переходит в клеточное ядро, где взаимодействует со специфическими участками ДНК (GREs) генов-мишеней глюкокортикоидов, влияя на интенсивность их транскрипции. Затем свободный от гормона ГР выходит из клеточного ядра в цитоплазму, завершая ядерно-цитоплазматический цикл этого белка. Согласно современным представлениям, существуют также внутриядерные хроматиновый и шапероновый циклы ГР. Хроматиновым циклом называется цикл связывания/диссоциации/повторного связывания гормонрецепторных комплексов с GREs, занимающий от нескольких секунд до нескольких десятков секунд. Шапероновый цикл происходит после диссоциации гормон-рецепторного комплекса в ядрах, когда ГР связывается с присутствующими в них теми же молекулярными шаперонами, которые взаимодействуют с этим белком в цитоплазме, и в результате чего вновь связывает гормон, затем высвобождается из комплекса с шаперонами и снова взаимодействует с GREs. Предполагается, что главным образом за счет существования шаперонового цикла ГР удерживается в ядре клетки в течение нескольких часов. В настоящем обзоре обобщены имеющиеся в литературе данные, на основании которых были построены модели хроматинового и внутриядерного шаперонового циклов ГР и проведен их критический анализ.

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