Isoform-specific Intermolecular Disulfide Bond Formation of Heterochromatin Protein 1 (HP1)
Isoform-specific Intermolecular Disulfide Bond Formation of Heterochromatin Protein 1 (HP1)
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DOI：
10.1074/jbc.m110.155788
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发表时间：
2010-10-08
影响因子：
4.8
通讯作者：
Takashima, Seiji
中科院分区：
文献类型：
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作者：
Higo, Shuichiro;Asano, Yoshihiro;Takashima, Seiji
异染色质蛋白1（HP1）的三种哺乳动物亚型，α，β和γ，在基因调控中发挥不同的作用。尽管它们的结构相似，这些异构体的不同功能意味着它们还受到翻译后修饰的调节。在这里，我们已经确定了分子间的二硫键形成的HP1半胱氨酸的亚型特异性的方式。HP1 α中的半胱氨酸133和HP1 γ中的半胱氨酸177参与分子间同源二聚化。虽然HP 1 α和HP 1 γ都含有反应性半胱氨酸残基，但只有HP 1 γ在氧化条件下容易且可逆地形成二硫化物同源二聚体。氧化二聚化的HP 1 γ与通用转录辅阻遏物TIF 1 β强烈且短暂地相互作用。在氧化条件下，HP 1 γ二聚化并将TIF 1 β保持在染色质组分中，并抑制其抑制能力。我们的研究结果突出了一个新的，异构体特异性的作用HP1作为传感器的细胞氧化还原状态。
Three mammalian isoforms of heterochromatin protein 1 (HP1), alpha, beta, and gamma, play diverse roles in gene regulation. Despite their structural similarity, the diverse functions of these isoforms imply that they are additionally regulated by post-translational modifications. Here, we have identified intermolecular disulfide bond formation of HP1 cysteines in an isoform-specific manner. Cysteine 133 in HP1 alpha and cysteine 177 in HP1 gamma were involved in intermolecular homodimerization. Although both HP1 alpha and HP1 gamma contain reactive cysteine residues, only HP1 gamma readily and reversibly formed disulfide homodimers under oxidative conditions. Oxidatively dimerized HP1 gamma strongly and transiently interacted with TIF1 beta, a universal transcriptional co-repressor. Under oxidative conditions, HP1 gamma dimerized and held TIF1 beta in a chromatin component and inhibited its repression ability. Our results highlight a novel, isoform-specific role for HP1 as a sensor of the cellular redox state.