A functional reference map of the RNF8 interactome in cancer.
A functional reference map of the RNF8 interactome in cancer.
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癌症中 RNF8 相互作用组的功能参考图
DOI：
10.1186/s13062-022-00331-z
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发表时间：
2022-07-13
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
RNF8是一种E3连接酶，被认为是一种关键的DNA损伤反应蛋白。近年来，多项研究表明，RNF8可作为肿瘤化疗/放射治疗的重要靶点。然而，由于缺乏RNF8的相互作用组参考图谱和对不同癌症中RNF8的全面分析，对RNF8的了解仍然有限，这突显了通过高通量方法绘制RNF8相互作用组图的必要性。设计了一种基于LC-MS的双向鉴定方法，用于高特异性的RNF8相互作用组的鉴定。通过电子计算机分析和体外验证，我们确定了一个新的RNF8相互作用组网络参考图谱，其中包含了许多新的靶点，如YBX1、DNMT1和HDCA1，新的生物学功能以及RNF8的基因与疾病的关联。我们的结果揭示了RNF8与神经退行性疾病或肿瘤浸润性免疫细胞之间的密切关系，这是基于批量RNA-seq和scRNA-seq数据集。作为我们交互作用组图概念的证明，我们验证了RNF8与YBX1之间的直接结合，并表明RNF8催化了YBX1的泛素化。这些结果表明，RNF8可能是YBX1的重要调控因子。我们的工作为寻求更好地探索或理解RNF8调节的癌症生物学功能的研究人员和临床医生提供了一个独特的框架。本研究有望为肿瘤抗RNF8治疗的合理设计和进一步开发提供参考。网上版载有补充材料，可在10.1186/s13062-022-00331-z查阅。
RNF8 is an E3 ligase identified as a critical DNA damage-responsive protein. Recently, multiple reports have shown that RNF8 could be used as an important therapeutic target for cancer chemo/radiotherapy. However, the understanding of RNF8 remains limited due to the lack of its interactome reference map and comprehensive analysis of RNF8 in diverse cancers, which underscores the need to map the interactome of RNF8 via high-throughput methods. A two-way identification method based on LC–MS was designed for the identification of the RNF8 interactome with high-specificity. By in silico analysis and in vitro validation, we identified a new reference map of the RNF8 interactome network containing many new targets, such as YBX1, DNMT1, and HDCA1, new biological functions and the gene-disease associations of RNF8. Our results revealed a close relationship between RNF8 and neurodegenerative diseases or tumor-infiltrating immune cells using bulk RNA-seq and scRNA-seq datasets. As a proof of concept of our interactome map, we validated the direct binding between RNF8 and YBX1 and showed that RNF8 catalyzed the ubiquitination of YBX1. These results demonstrated that RNF8 might be a crucial regulator of YBX1. Our work provides a unique framework for researchers and clinicians who seek to better explore or understand RNF8-regulated biological functions in cancers. This study will hopefully facilitate the rational design and further development of anti-RNF8 therapy in cancers. The online version contains supplementary material available at 10.1186/s13062-022-00331-z.
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影响因子：
16.6
作者：
Lee CC;Lin JC;Hwang WL;Kuo YJ;Chen HK;Tai SK;Lin CC;Yang MH
通讯作者：
Yang MH
RNF8促进乳腺癌细胞上皮间质转化
DOI：
10.1186/s13046-016-0363-6
发表时间：
2016-06-04
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Kuang J;Li L;Guo L;Su Y;Wang Y;Xu Y;Wang X;Meng S;Lei L;Xu L;Shao G
通讯作者：
Shao G
影响因子：
48
作者：
Li T;Wernersson R;Hansen RB;Horn H;Mercer J;Slodkowicz G;Workman CT;Rigina O;Rapacki K;Stærfeldt HH;Brunak S;Jensen TS;Lage K
通讯作者：
Lage K
影响因子：
64.5
作者：
Goodarzi H;Liu X;Nguyen HC;Zhang S;Fish L;Tavazoie SF
通讯作者：
Tavazoie SF
影响因子：
4.4
作者：
Koch A;De Meyer T;Jeschke J;Van Criekinge W
通讯作者：
Van Criekinge W