文献类型：期刊文献

英文题名：Arginine methylation-dependent stabilization of SUV39H1 promotes breast cancer growth

作者：Zhao, Wei[1];Wang, Ge[1];Wang, Peng[1,2];Ma, Bo[3];Liu, Bo[1];Fu, Yenan[1];Tang, Youzhi[1];Duan, Xinwei[1];Zhou, Kunhao[1];Zhang, Jing[1];Zhu, Wei-Guo[4];Zhang, Hongquan[1];Yu, Yu[1]

第一作者：Zhao, Wei

通信作者：Zhang, HQ[1];Yu, Y[1];Zhu, WG[2]

机构：[1]Peking Univ, PKU Int Canc Inst, Sch Basic Med Sci, Dept Human Anat Histol & Embryol,Hlth Sci Ctr, Beijing, Peoples R China;[2]Gansu Univ Chinese Med, Sch Tradit Chinese & Western Med, Lanzhou, Peoples R China;[3]Chinese Acad Med Sci & Peking Union Med Coll, Inst Mat Med, State Key Lab Bioact Subst & Funct Nat Med, Beijing, Peoples R China;[4]Shenzhen Univ, Med Sch, Guangdong Key Lab Genome Instabil & Human Dis Prev, Int Canc Ctr, Shenzhen, Peoples R China

第一机构：Peking Univ, PKU Int Canc Inst, Sch Basic Med Sci, Dept Human Anat Histol & Embryol,Hlth Sci Ctr, Beijing, Peoples R China

通信机构：[1]corresponding author), Peking Univ, PKU Int Canc Inst, Sch Basic Med Sci, Dept Human Anat Histol & Embryol,Hlth Sci Ctr, Beijing, Peoples R China;[2]corresponding author), Shenzhen Univ, Med Sch, Guangdong Key Lab Genome Instabil & Human Dis Prev, Int Canc Ctr, Shenzhen, Peoples R China.

年份：2026

卷号：45

期号：14

起止页码：1220

外文期刊名：ONCOGENE

收录：;Scopus(收录号：2-s2.0-105034296692);WOS:【SCI-EXPANDED(收录号:WOS:001711528200001)】；

基金：This work was supported by grants from Ministry of Science and Technology of the People's Republic of China 2025ZD0544700 and 2022YFA1104003 (H.Z.), National Natural Science Foundation of China 82372992 and 82073076 (Y.Y.), and National Natural Science Foundation of China 82230094 (H.Z.), Michigan Medicine-PKUHSC Joint Institute for Translational and Clinical Research 2024SQGH002235.

语种：英文

摘要：Suppressors of variegation 3-9 homolog 1 (SUV39H1), the enzyme responsible for establishing histone H3 lysine 9 trimethylation (H3K9me3) marks in heterochromatin, is frequently dysregulated in cancers. However, the mechanisms underlying SUV39H1 dysregulation in breast cancer remain largely unclear. Here, we report that protein arginine methyltransferase 1 (PRMT1) directly interacts with SUV39H1 and dimethylates it at arginine 378 (R378). PKC signaling-mediated phosphorylation of SUV39H1 at S391 enhances this interaction, thereby promoting its methylation. Notably, PRMT1 binds to SUV39H1 with higher affinity and binding free energy than MDM2, causing a structural clash that blocks MDM2-mediated ubiquitination of SUV39H1. Moreover, methylated SUV39H1 exhibits enhanced H3K9me3 methyltransferase activity and promotes tumor cell growth. A SUV39H1-derived peptide (TAT-SUV-peptide) disrupts the interaction between PRMT1 and SUV39H1, thereby reducing SUV39H1 methylation. Administration of TAT-SUV-peptide remarkably suppresses mammary tumor growth. Taken together, our findings reveal a critical phosphorylation-methylation-ubiquitination axis in controlling SUV39H1 stability and highlight its therapeutic potential through targeting SUV39H1 methylation.