研究动态
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赖氨酸特异性甲基转移酶 Set7/9 在干性、分化和发育中的作用。

Lysine-specific methyltransferase Set7/9 in stemness, differentiation, and development.

发表日期:2024 May 29
作者: Alexandra Daks, Sergey Parfenyev, Oleg Shuvalov, Olga Fedorova, Alexander Nazarov, Gerry Melino, Nickolai A Barlev
来源: Cellular & Molecular Immunology

摘要:

执行蛋白质翻译后修饰 (PTM) 的酶形成了关键的翻译后调节电路,可协调生物体中的所有细胞过程。特别是,细胞干性和分化之间的平衡对于多细胞生物的发育至关重要。重要的是,这种平衡在基因水平上的微调很大程度上是由组蛋白的特定 PTM(包括赖氨酸甲基化)介导的。赖氨酸甲基化是通过特殊酶(赖氨酸甲基转移酶)进行的,这些酶将甲基从 S-腺苷-L-甲硫氨酸转移到蛋白质底物的赖氨酸残基上。 Set7/9 是示例性蛋白质甲基转移酶之一,但尚未得到充分研究。它最初被发现为组蛋白 H3 赖氨酸 4 特异性甲基转移酶,后来被证明可以甲基化许多非组蛋白,这些蛋白是干性和分化的关键调节因子,包括 p53、pRb、YAP、DNMT1、SOX2、FOXO3 等。在这篇综述中,我们总结了迄今为止关于 Set7/9 在胚胎发生和成体生物体中细胞分化和组织发育中的作用的信息。最后,我们强调并讨论了 Set7/9 在与异常细胞分化和自我更新相关的病理过程中的作用,包括癌症干细胞的形成。© 2024。作者。
The enzymes performing protein post-translational modifications (PTMs) form a critical post-translational regulatory circuitry that orchestrates literally all cellular processes in the organism. In particular, the balance between cellular stemness and differentiation is crucial for the development of multicellular organisms. Importantly, the fine-tuning of this balance on the genetic level is largely mediated by specific PTMs of histones including lysine methylation. Lysine methylation is carried out by special enzymes (lysine methyltransferases) that transfer the methyl group from S-adenosyl-L-methionine to the lysine residues of protein substrates. Set7/9 is one of the exemplary protein methyltransferases that however, has not been fully studied yet. It was originally discovered as histone H3 lysine 4-specific methyltransferase, which later was shown to methylate a number of non-histone proteins that are crucial regulators of stemness and differentiation, including p53, pRb, YAP, DNMT1, SOX2, FOXO3, and others. In this review we summarize the information available to date on the role of Set7/9 in cellular differentiation and tissue development during embryogenesis and in adult organisms. Finally, we highlight and discuss the role of Set7/9 in pathological processes associated with aberrant cellular differentiation and self-renewal, including the formation of cancer stem cells.© 2024. The Author(s).