Global characterization of proteome and lysine methylome features in EZH2 wild-type and mutant lymphoma cell lines.
Global characterization of proteome and lysine methylome features in EZH2 wild-type and mutant lymphoma cell lines.
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EZH2 野生型和突变型淋巴瘤细胞系中蛋白质组和赖氨酸甲基化组特征的整体表征。
DOI：
10.1016/j.jprot.2019.103614
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发表时间：
2020
影响因子：
3.3
通讯作者：
Tan Minjia
中科院分区：
文献类型：
--
作者：
Hao Bingbing;Sun Mingwei;Zhang Min;Zhao Xiaoxiao;Zhao Lei;Li Bolin;Zhai Linhui;Liu Ping;Hu Hao;Xu Jun-Yu;Tan Minjia
赖氨酸甲基化是一种广泛存在的蛋白质翻译后修饰，在多种细胞过程中具有重要意义。EZH2是一种甲基转移酶，可以特异性地三甲基化组蛋白H3的赖氨酸27，它在几种癌症中的异常促进了它对血液肿瘤的抑制剂的发展。在这项研究中，我们对EZH2野生型和Y641突变型淋巴瘤细胞系中赖氨酸单甲基、二甲基和三甲基进行了深入的研究。我们的研究结果表明，几种底物在不同的甲基化水平上被修饰。此外，这些甲基化的赖氨酸残基也可能经历其他类型的ptm。结合蛋白质表达、赖氨酸乙酰化、赖氨酸泛素化和蛋白n端乙酰化水平的差异，我们的研究强调了赖氨酸甲基化的底物特异性及其与其他类型PTMs的串扰。总之，我们的研究对血液细胞系的整体细胞甲基化特征有了新的认识，为进一步研究赖氨酸甲基化的分布和功能提供了新的视角。我们的研究显示了ezh2异常DLBCL细胞系中单甲基化、二甲基化和三甲基化的全球格局，揭示了赖氨酸甲基化的分子特征。结合不同类型PTMs之间的蛋白丰度和潜在的串扰，我们的研究为血液肿瘤的整体细胞甲基化特征提供了新的见解，并进一步研究了赖氨酸甲基化的分布和功能。
Lysine methylation is a widespread protein post-translational modification showing essentialities in versatile cellular process. EZH2, a methyltransferase specifically trimethylates the lysine 27 of histone H3 and its aberrance in several cancers promotes the development of its inhibitors against hematological tumors. In this study, we presented a deep exploration of lysine mono-, di- and trimethylomes in EZH2 wild-type and Y641 mutant lymphoma cell lines. Our results showed that several substrates were modified in different methylation levels. Moreover, these methylated lysine residues could also undergo other types of PTMs. Combined with the differences proved in protein expression, lysine acetylation, lysine ubiquitylation and protein N-termianl acetylation level, our study underlined the substrate specificity of lysine methylation and its crosstalk with other types of PTMs. Totally, our study raised new insights into the global cellular methylation features in hematological cell lines, which provided further inspects into the distribution and function of lysine methylation.SignificanceOur study showed the global landscape of mono-, di- and trimethylomes in the EZH2-aberrant DLBCL cell lines, revealing the molecular characteristics of lysine methylation. Combined with the protein abundance and potential crosstalk among different types of PTMs, our study raised new insights into the global cellular methylation features in hematological tumors and provided further inspects into the distribution and function of lysine methylation.