Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers
RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/29511 |
| _version_ | 1811235939233562624 |
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| author | Xuehui Hong He Huang Xingfeng Qiu Zhijie Ding Xing Feng Yuekun Zhu Huiqin Zhuo Jingjing Hou Jiabao Zhao Wangyu Cai Ruihua Sha Xinya Hong Yongxiang Li Hongjiang Song Zhiyong Zhang |
| author_facet | Xuehui Hong He Huang Xingfeng Qiu Zhijie Ding Xing Feng Yuekun Zhu Huiqin Zhuo Jingjing Hou Jiabao Zhao Wangyu Cai Ruihua Sha Xinya Hong Yongxiang Li Hongjiang Song Zhiyong Zhang |
| author_sort | Xuehui Hong |
| collection | DOAJ |
| description | RIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. Functional experiments demonstrate the RIOK1 methylation reduces the tumor growth and metastasis in mice model. Importantly, the protein levels of CK2 and LSD1 show an inverse correlation with FBXO6 and SETD7 expression in human colorectal cancer tissues. Together, this study highlights the importance of a RIOK1 methylation-phosphorylation switch in determining colorectal and gastric cancer development. |
| first_indexed | 2024-04-12T12:00:46Z |
| format | Article |
| id | doaj.art-e5d3e367fa1b4ad5ade7856df54141ac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T12:00:46Z |
| publishDate | 2018-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e5d3e367fa1b4ad5ade7856df54141ac2022-12-22T03:33:52ZengeLife Sciences Publications LtdeLife2050-084X2018-01-01710.7554/eLife.29511Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancersXuehui Hong0He Huang1Xingfeng Qiu2Zhijie Ding3Xing Feng4Yuekun Zhu5Huiqin Zhuo6Jingjing Hou7Jiabao Zhao8Wangyu Cai9Ruihua Sha10Xinya Hong11Yongxiang Li12Hongjiang Song13Zhiyong Zhang14https://orcid.org/0000-0001-8576-1607Longju Medical Research Center, Key Laboratory of Basic Pharmacology, Ministry of Education, Zunyi Medical College, Zunyi, China; Department of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China; Digestive Cancer Laboratory, Second Affiliated Hospital of Xinjiang Medical University, Urumqi, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Radiation Oncology, Cancer Institute of New Jersey, Rutgers University, New Brunswick, United StatesDepartment of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Gastrointestinal Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China; Institute of Gastrointestinal Oncology, Medical College of Xiamen University, Xiamen, China; Xiamen Municipal Key Laboratory of Gastrointestinal Oncology, Xiamen, ChinaDepartment of Digestive Disease, Hongqi Hospital, Mudanjiang Medical University, Mudanjiang, ChinaDepartment of Medical Imaging and Ultrasound, Zhongshan Hospital of Xiamen University, Xiamen, Fujian, ChinaDepartment of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, ChinaDepartment of General Surgery, The Third Affiliated Hospital of Harbin Medical University, Harbin, ChinaLongju Medical Research Center, Key Laboratory of Basic Pharmacology, Ministry of Education, Zunyi Medical College, Zunyi, China; Department of Surgery, Robert-Wood-Johnson Medical School University Hospital, Rutgers University, The State University of New Jersey, New Brunswick, United StatesRIOK1 has recently been shown to play important roles in cancers, but its posttranslational regulation is largely unknown. Here we report that RIOK1 is methylated at K411 by SETD7 methyltransferase and that lysine-specific demethylase 1 (LSD1) reverses its methylation. The mutated RIOK1 (K411R) that cannot be methylated exhibits a longer half-life than does the methylated RIOK1. FBXO6 specifically interacts with K411-methylated RIOK1 through its FBA domain to induce RIOK1 ubiquitination. Casein kinase 2 (CK2) phosphorylates RIOK1 at T410, which stabilizes RIOK1 by antagonizing K411 methylation and impeding the recruitment of FBXO6 to RIOK1. Functional experiments demonstrate the RIOK1 methylation reduces the tumor growth and metastasis in mice model. Importantly, the protein levels of CK2 and LSD1 show an inverse correlation with FBXO6 and SETD7 expression in human colorectal cancer tissues. Together, this study highlights the importance of a RIOK1 methylation-phosphorylation switch in determining colorectal and gastric cancer development.https://elifesciences.org/articles/29511RioK1FBXO6methylationcolorectal cancerSETD7Casein Kinase 2 |
| spellingShingle | Xuehui Hong He Huang Xingfeng Qiu Zhijie Ding Xing Feng Yuekun Zhu Huiqin Zhuo Jingjing Hou Jiabao Zhao Wangyu Cai Ruihua Sha Xinya Hong Yongxiang Li Hongjiang Song Zhiyong Zhang Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers eLife RioK1 FBXO6 methylation colorectal cancer SETD7 Casein Kinase 2 |
| title | Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers |
| title_full | Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers |
| title_fullStr | Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers |
| title_full_unstemmed | Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers |
| title_short | Targeting posttranslational modifications of RIOK1 inhibits the progression of colorectal and gastric cancers |
| title_sort | targeting posttranslational modifications of riok1 inhibits the progression of colorectal and gastric cancers |
| topic | RioK1 FBXO6 methylation colorectal cancer SETD7 Casein Kinase 2 |
| url | https://elifesciences.org/articles/29511 |
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