Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration

Yao,Ruosi; Wang,Yingli; Han,Danyang; Ma,Yuhui; Ma,Musong; Zhao,Yaping; Tan,Jiang; Lu,Jun; Xu,Guiying; Li,Xiaoxue

doi:10.3892/or.2018.6669

Lysines 207 and 325 methylation of WDR5 catalyzed by SETD6 promotes breast cancer cell proliferation and migration

Authors:
- Ruosi Yao
- Yingli Wang
- Danyang Han
- Yuhui Ma
- Musong Ma
- Yaping Zhao
- Jiang Tan
- Jun Lu
- Guiying Xu
- Xiaoxue Li
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Affiliations: Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, P.R. China, Department of Toxicology, Jilin Province Institution of Tumor Research, Changchun, Jilin 130000, P.R. China, Department of Hematology, Blood Diseases Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221004, P.R. China, Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, P.R. China, Department of Breast Surgery, Tumor Hospital of Jilin Province, Changchun, Jilin 130000, P.R. China
Published online on: August 23, 2018 https://doi.org/10.3892/or.2018.6669
Pages: 3069-3077

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Abstract

Accumulating evidence has revealed that the methylation of lysines on nonhistones by histone lysine methyltransferases (HMTs) is crucial for regulating tumorigenesis and metastasis. However, whether the methylation of lysines on HMT complex components occurs and has functions in cancer progression is less well understood. WD repeat domain 5 (WDR5) is a core component of an HMT complex named mixed lineage leukemia (MLL)/Suppressor of Variegation, Enhancer of Zeste, and Trithorax 1 (SET1). In the present study, it was reported that lysines 207 and 325 (K207 and K325, respectively) of WDR5 were monomethylated by SET‑domain‑containing protein methyltransferase 6. Disrupting the methylation of K207/K325 via a K207R/K325R double‑site mutation attenuated the WDR5 promotion of breast cancer cell proliferation and migration. Methylation of K207/K325 on WDR5 partially contributed to maintaining global histone tri‑methylation of lysine 4 on histone H3 levels, but did not affect MLL/SET1 complex assembly. These results further understanding of a potential post‑translational modification of WDR5, and imply that the methylation of lysines on HMT complex components is crucial for regulating human carcinogenesis.

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