Role of histone deacetylase 2 and its posttranslational modifications in cardiac hypertrophy
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Cardiac hypertrophy is a form of global remodeling, althoughthe initial step seems to be an adaptation to increased hemodynamicdemands. The characteristics of cardiac hypertrophyinclude the functional reactivation of the arrested fetal geneprogram, where histone deacetylases (HDACs) are closely linkedin the development of the process. To date, mammalianHDACs are divided into four classes: I, II, III, and IV. By structuralsimilarities, class II HDACs are then subdivided into IIaand IIb. Among class I and II HDACs, HDAC2, 4, 5, and 9 havebeen reported to be involved in hypertrophic responses; HDAC4,5, and 9 are negative regulators, whereas HDAC2 is a pro-hypertrophicmediator. The molecular function and regulation ofclass IIa HDACs depend largely on the phosphorylation-mediatedcytosolic redistribution, whereas those of HDAC2 takeplace primarily in the nucleus. In response to stresses, posttranslationalmodification (PTM) processes, dynamic modificationsafter the translation of proteins, are involved in the regulationof the activities of those hypertrophy-related HDACs. Inthis article, we briefly review 1) the activation of HDAC2 inthe development of cardiac hypertrophy and 2) the PTM ofHDAC2 and its implications in the regulation of HDAC2activity.
Abstract
Cardiac hypertrophy is a form of global remodeling, althoughthe initial step seems to be an adaptation to increased hemodynamicdemands. The characteristics of cardiac hypertrophyinclude the functional reactivation of the arrested fetal geneprogram, where histone deacetylases (HDACs) are closely linkedin the development of the process. To date, mammalianHDACs are divided into four classes: I, II, III, and IV. By structuralsimilarities, class II HDACs are then subdivided into IIaand IIb. Among class I and II HDACs, HDAC2, 4, 5, and 9 havebeen reported to be involved in hypertrophic responses; HDAC4,5, and 9 are negative regulators, whereas HDAC2 is a pro-hypertrophicmediator. The molecular function and regulation ofclass IIa HDACs depend largely on the phosphorylation-mediatedcytosolic redistribution, whereas those of HDAC2 takeplace primarily in the nucleus. In response to stresses, posttranslationalmodification (PTM) processes, dynamic modificationsafter the translation of proteins, are involved in the regulationof the activities of those hypertrophy-related HDACs. Inthis article, we briefly review 1) the activation of HDAC2 inthe development of cardiac hypertrophy and 2) the PTM ofHDAC2 and its implications in the regulation of HDAC2activity.
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