Arginine and lysine methylation of MRPS23 promotes breast cancer metastasis 1 through regulating OXPHOS
Arginine and lysine methylation of MRPS23 promotes breast cancer metastasis 1 through regulating OXPHOS
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DOI：
10.1038/s41388-021-01785-7
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Jun Lu
中科院分区：
文献类型：
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作者：
Lingxia Liu;Xiliu Zhang;Huayi Ding;Donghui Cao;Xin Liu;Yingqi Liu;Jiwei Liu;Cong Lin;Na Zhang;Guannan Wang;Baiqu Huang;Yu Zhang;Jun Lu
Mitochondrial oxidative phosphorylation (OXPHOS) is a vital regulator of tumor metastasis. However, 46.the mechanisms governing OXPHOS to facilitate tumor metastasis remain unclear. In this study, we 47.discovered that arginine 21(R21) and lysine 108 (K108) of mitochondrial ribosomal protein S23 48.(MRPS23) was methylated by protein arginine methyltransferase 7 (PRMT7) and 49.SET-domain-containing protein 6 (SETD6), respectively. R21 methylation accelerated the 50.poly-ubiquitin-dependent degradation of MRPS23 to a low level. The MRPS23 degradation inhibited 51.OXPHOS with elevated mtROS level, which consequently increased breast cancer cell invasion and 52.metastasis. In contrast, K108 methylation increased MRPS23 stability, and K108 methylation 53.coordinated with R21 methylation to maintain a low level of MRPS23, which was in favor of 54.supporting breast cancer cell survival through regulating OXPHOS. Consistently, R21 and K108 55.methylation was correlated with the malignant breast carcinoma. Significantly, our findings unveil a 56.unique mechanism of controlling OXPHOS by arginine and lysine methylation, and point to the impact 57.of PRMT7-SETD6-MRPS23 axis during breast cancer metastasis.
