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HDAC6通过在lysine320处去乙化p53来保持BNIP3表达和线粒体完整性

Se-In Lee¹, Yuri Seo¹, Hoang Thi Oanh¹

¹Graduate School of Analytical Science and Technology (GRAST), Chungnam National University, Daejeon, 305-764, Republic of Korea.

Biochemical and biophysical research communications

|December 3, 2023

概括

海斯脱乙酶6 (HDAC6) 调节K320的p53乙化,影响线粒细胞衰变和线粒体结构. 失去HDAC6会影响BNIP3的表达,导致线粒体异常,特别是在神经元中.

科学领域:

细胞生物学细胞生物学
神经科学是一个神经科学.
生物化学生物化学

背景情况:

基因组脱乙酶6 (HDAC6) 在多个部位脱乙p53,影响亡和瘤抑制.
之前的研究表明,K320的p53乙化增加了HDAC6-废除的小鼠肝脏.
对于p53 K320乙化的生物影响尚不清楚.

研究的目的:

研究HDAC6脱乙酶活性在调节p53 K320乙化中的作用.
阐明p53 K320乙化的生物后果,特别是在大脑中.
为了确定HDAC6,p53乙化,线粒体和线粒体完整性之间的联系.

主要方法:

使用HDAC6淘汰赛小鼠模型和MEF (小鼠胚胎纤维细胞).
在K320和BNIP3表达水平评估了p53乙化,通过西式涂抹和其他生物化学测试.
采用K320R突变的p53来模仿脱甲基化,并观察其对BNIP3表达的影响.
从HDAC6淘汰赛小鼠中检查神经元中的线粒体形态.

主要成果:

与其他组织相比,HDAC6淘汰赛小鼠大脑显示出明显更高的p53 K320乙化.
p53 K320的乙化水平与BNIP3表达相反相关.
在K320R突变p53过度表达后,在HDAC6淘汰赛MEF中观察到BNIP3表达的恢复.
缺少HDAC6的神经元表现出减少BNIP3表达,并积累了异常线粒体与胀的晶状体.

结论:

在K320部位调节p53乙化时,HDAC6脱乙酶活性至关重要.
在K320中对p53进行HDAC6介导的脱乙基化对于维持BNIP3表达至关重要.
这一途径对于线粒体和维护线粒体结构完整性至关重要,神经元对HDAC6损失特别脆弱.

关键词:

乙化乙化是一种在BNIP3中,BNIP3是BNP3.在 HDAC6 中.线粒体中的线粒体.在 p53 里,p53 是一个 p53 的类型.

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