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希斯甲基转移酶活性影响人类细胞的新陈代谢,独立于转录调节

Marcos Francisco Perez^1,2, Peter Sarkies¹

¹Department of Biochemistry, University of Oxford, Oxford, United Kingdom.

|October 26, 2023

概括

希斯甲基化希斯甲基化

科学领域:

生物化学生物化学
分子生物学分子生物学
癌症研究癌症研究

背景情况:

细胞基因素N端尾部经历了翻译后的修改,主要影响转录调节.
这些酶修饰对更广泛的代谢调节的影响仍然不太清楚.

研究的目的:

为了研究素甲基化对细胞代谢的影响.
探索基因组甲基转移酶 (HMTs),甲基沉积和癌症和健康组织中的S-腺甲 (SAM) 代谢之间的关系.

主要方法:

利用代谢学,蛋白学和RNA测序在癌细胞系,原发性瘤和健康组织上.
分析了HMT表达,NNMT和PEMT活性以及基因素标记之间的相关性.
研究了视网母细胞瘤 (Rb) 瘤抑制剂在HMT共同调节中的作用.

主要成果:

在癌症中,HMT表达与NNMT活性相反相关,NNMT是S-adenosyl metionin (SAM) 的甲基沉.
在健康的组织中,组织组织甲基化与PEMT活性相反相关,这是一个替代的甲基沉积体.
在Rb突变癌症中,HMT活性增加,NNMT表达减少,独立于转录变化影响SAM代谢.

结论:

基因组甲基转移酶活性影响S-adenosyl metionin的新陈代谢,而不考虑直接的转录调节.
Rb瘤抑制剂与参与代谢和转录过程的HMTs共同调节.
研究结果揭示了基因素修饰酶与细胞代谢恒常之间的一种新的联系.

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