肌动蛋白组氨酸甲基转移酶SETD3是一种CHD1赖氨酸二甲基转移酶

IF 10.1 1区医学 Q1 ONCOLOGY

Cancer letters Pub Date : 2025-10-02 DOI:10.1016/j.canlet.2025.218073

Weilin Peng , Christopher Wang , Rui Yang , Xiong Peng , Zhenyu Zhao , Boxue He , Bei Qing , Qidong Cai , Wei Yin , Yichuan Chen , Fenglei Yu , Xiang Wang , Yongguang Tao

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引用次数: 0

摘要

蛋白质甲基化是一种广泛的翻译后修饰，主要针对赖氨酸、精氨酸和组氨酸残基。异常蛋白甲基化与肿瘤发生有关，尽管组氨酸甲基转移酶SETD3在癌症中的具体作用仍知之甚少。在这项研究中，我们发现CHD1是SETD3的一个新的底物，SETD3在赖氨酸209 （K209）处使CHD1二甲基化。该位点的二甲基化通过降低CHD1的泛素化而增强其稳定性。此外，SETD3介导CHD1甲基化，增强H3K4me3表观遗传标记，促进TNF-NFκB通路基因的转录激活。总之，我们的研究结果证实了CHD1是SETD3的新底物，并揭示了SETD3介导的K209位点CHD1二甲基化促进肿瘤进展的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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The Actin Histidine methyltransferase SETD3 is a CHD1 lysine di-methyltransferase

Protein methylation is a widespread posttranslational modification that primarily targets lysine, arginine, and histidine residues. Aberrant protein methylation has been implicated in tumorigenesis, although the specific role of SETD3, a histidine methyltransferase, in cancer remains poorly understood. In this study, we identify CHD1 as a novel substrate of SETD3, which dimethylates CHD1 at lysine 209 (K209). Dimethylation at this site enhances CHD1 protein stability by reducing its ubiquitination. Furthermore, SETD3 mediates methylation of CHD1 to enhance H3K4me3 epigenetic marks and promote transcriptional activation of TNF-NFκB pathway genes. Collectively, our findings establish CHD1 as a new substrate for SETD3 and reveal a mechanism by which SETD3-mediated dimethylation of CHD1 at K209 promotes tumor progression.

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来源期刊

Cancer letters 医学-肿瘤学

CiteScore

17.70

自引率

2.10%

发文量

427

审稿时长

15 days

期刊介绍： Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research. Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy. By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.