The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer.
The NFIB/CARM1 partnership is a driver in preclinical models of small cell lung cancer.
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DOI：
10.1038/s41467-023-35864-y
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发表时间：
2023-01-23
影响因子：
16.6
通讯作者：
Bedford, Mark T.
中科院分区：
文献类型：
--
作者：
Gao, Guozhen;Hausmann, Simone;Flores, Natasha M.;Benitez, Ana Morales;Shen, Jianjun;Yang, Xiaojie;Person, Maria D.;Gayatri, Sitaram;Cheng, Donghang;Lu, Yue;Liu, Bin;Mazur, Pawel K.;Bedford, Mark T.
辅助激活因子相关精氨酸甲基转移酶（CARM1）顾名思义促进转录。它是通过修饰组蛋白和染色质结合蛋白来实现的。我们确定了核因子IB （NFIB）是CARM1底物，并表明该转录因子利用CARM1作为辅激活因子。生化研究表明TRIM29是NFIB甲基化的效应分子。重要的是，NFIB具有致癌和转移活性，并且在小细胞肺癌（SCLC）中经常过度表达。在这里，我们探讨了NFIB的CARM1甲基化对其转化活性的重要可能性。通过SCLC小鼠模型，我们发现CARM1和NFIB上的CARM1甲基化位点对SCLC的快速发病都是至关重要的。此外，CARM1和甲基化的NFIB负责在肿瘤中维持类似的开放染色质状态。总之，这些发现表明CARM1可能是SCLC的治疗靶点。蛋白精氨酸甲基化可促进肿瘤进展。本文作者表明，蛋白精氨酸甲基转移酶CARM1甲基化转录因子NFIB，促进小细胞肺癌的生长。
The coactivator associated arginine methyltransferase (CARM1) promotes transcription, as its name implies. It does so by modifying histones and chromatin bound proteins. We identified nuclear factor I B (NFIB) as a CARM1 substrate and show that this transcription factor utilizes CARM1 as a coactivator. Biochemical studies reveal that tripartite motif 29 (TRIM29) is an effector molecule for methylated NFIB. Importantly, NFIB harbors both oncogenic and metastatic activities, and is often overexpressed in small cell lung cancer (SCLC). Here, we explore the possibility that CARM1 methylation of NFIB is important for its transforming activity. Using a SCLC mouse model, we show that both CARM1 and the CARM1 methylation site on NFIB are critical for the rapid onset of SCLC. Furthermore, CARM1 and methylated NFIB are responsible for maintaining similar open chromatin states in tumors. Together, these findings suggest that CARM1 might be a therapeutic target for SCLC. Protein arginine methylation can contribute to tumor progression. Here the authors show that protein arginine methyltransferase, CARM1, methylates transcription factor NFIB to promote the growth of small cell lung cancers.
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