Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification.
Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification.
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DOI：
10.1186/s13046-022-02338-w
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发表时间：
2022-04-15
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--
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代谢物是多种酶催化细胞代谢的中间产物。代谢重塑作为癌细胞的生化指纹，会导致代谢产物异常蓄积。这些代谢物主要通过非共价相互作用产生能量或作为信号转导媒介。随着高灵敏质谱学技术的发展，各种代谢物被证明通过赖氨酸酰化的形式对蛋白质进行共价修饰，包括赖氨酸乙酰化、巴豆化、乳糖化、琥珀酸化、丙酰化、丁酰化、丙二酸化、戊二酸化、2-羟基异丁酰化和β-羟丁酰化。这些修饰可以调节基因表达和细胞内信号通路，突出代谢物的广泛作用。由于赖氨酸乙酰化已被广泛研究，因此在本综述中未作详细讨论。我们重点介绍了上述9种乙酰化以外的新的赖氨酸酰化反应，它们可以分为两类：组蛋白酰化反应和非组蛋白酰化反应。我们总结了这些酰化类型的特征和共同功能，最重要的是，提供了它们对肿瘤发生的微调控制以及在肿瘤诊断、监测和治疗中的潜在价值。
Metabolites are intermediate products of cellular metabolism catalysed by various enzymes. Metabolic remodelling, as a biochemical fingerprint of cancer cells, causes abnormal metabolite accumulation. These metabolites mainly generate energy or serve as signal transduction mediators via noncovalent interactions. After the development of highly sensitive mass spectrometry technology, various metabolites were shown to covalently modify proteins via forms of lysine acylation, including lysine acetylation, crotonylation, lactylation, succinylation, propionylation, butyrylation, malonylation, glutarylation, 2-hydroxyisobutyrylation and β-hydroxybutyrylation. These modifications can regulate gene expression and intracellular signalling pathways, highlighting the extensive roles of metabolites. Lysine acetylation is not discussed in detail in this review since it has been broadly investigated. We focus on the nine aforementioned novel lysine acylations beyond acetylation, which can be classified into two categories: histone acylations and nonhistone acylations. We summarize the characteristics and common functions of these acylation types and, most importantly, provide a glimpse into their fine-tuned control of tumorigenesis and potential value in tumour diagnosis, monitoring and therapy.
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