CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis
Identifieur interne : 000198 ( Main/Exploration ); précédent : 000197; suivant : 000199CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis
Auteurs : Chaohua Liu [République populaire de Chine] ; Qiaoyan Yang [République populaire de Chine] ; Qian Zhu [République populaire de Chine] ; Xiaopeng Lu [République populaire de Chine] ; Meiting Li [République populaire de Chine] ; Tianyun Hou [République populaire de Chine] ; Zhiming Li [République populaire de Chine] ; Ming Tang [République populaire de Chine] ; Yinglu Li [République populaire de Chine] ; Hui Wang [République populaire de Chine] ; Yang Yang [République populaire de Chine] ; Haiying Wang [République populaire de Chine] ; Ying Zhao [République populaire de Chine] ; He Wen [République populaire de Chine] ; Xiangyu Liu [République populaire de Chine] ; Zebin Mao [République populaire de Chine] ; Wei-Guo Zhu [République populaire de Chine]Source :
- Theranostics [ 1838-7640 ] ; 2020.
Abstract
Url:
DOI: 10.7150/thno.39013
PubMed: 32042335
PubMed Central: 6993218
Affiliations:
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type="RBID">PMC:6993218</idno><idno type="doi">10.7150/thno.39013</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000826</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000826</idno><idno type="wicri:Area/Pmc/Curation">000826</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000826</idno><idno type="wicri:Area/Pmc/Checkpoint">000182</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000182</idno><idno type="wicri:Area/Ncbi/Merge">000F17</idno><idno type="wicri:Area/Ncbi/Curation">000F17</idno><idno type="wicri:Area/Ncbi/Checkpoint">000F17</idno><idno type="wicri:Area/Main/Merge">000198</idno><idno type="wicri:Area/Main/Curation">000198</idno><idno type="wicri:Area/Main/Exploration">000198</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis</title><author><name sortKey="Liu, Chaohua" sort="Liu, Chaohua" uniqKey="Liu C" first="Chaohua" last="Liu">Chaohua Liu</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yang, Qiaoyan" sort="Yang, Qiaoyan" uniqKey="Yang Q" first="Qiaoyan" last="Yang">Qiaoyan Yang</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhu, Qian" sort="Zhu, Qian" uniqKey="Zhu Q" first="Qian" last="Zhu">Qian Zhu</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Lu, Xiaopeng" sort="Lu, Xiaopeng" uniqKey="Lu X" first="Xiaopeng" last="Lu">Xiaopeng Lu</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Meiting" sort="Li, Meiting" uniqKey="Li M" first="Meiting" last="Li">Meiting Li</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Hou, Tianyun" sort="Hou, Tianyun" uniqKey="Hou T" first="Tianyun" last="Hou">Tianyun Hou</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Li, Zhiming" sort="Li, Zhiming" uniqKey="Li Z" first="Zhiming" last="Li">Zhiming Li</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Tang, Ming" sort="Tang, Ming" uniqKey="Tang M" first="Ming" last="Tang">Ming Tang</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Li, Yinglu" sort="Li, Yinglu" uniqKey="Li Y" first="Yinglu" last="Li">Yinglu Li</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wang, Haiying" sort="Wang, Haiying" uniqKey="Wang H" first="Haiying" last="Wang">Haiying Wang</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Wen, He" sort="Wen, He" uniqKey="Wen H" first="He" last="Wen">He Wen</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Liu, Xiangyu" sort="Liu, Xiangyu" uniqKey="Liu X" first="Xiangyu" last="Liu">Xiangyu Liu</name><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author><author><name sortKey="Mao, Zebin" sort="Mao, Zebin" uniqKey="Mao Z" first="Zebin" last="Mao">Zebin Mao</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Zhu, Wei Guo" sort="Zhu, Wei Guo" uniqKey="Zhu W" first="Wei-Guo" last="Zhu">Wei-Guo Zhu</name><affiliation wicri:level="1"><nlm:aff id="A1">Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191</wicri:regionArea><placeName><settlement type="city">Pékin</settlement></placeName></affiliation><affiliation wicri:level="1"><nlm:aff id="A2">Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Guangdong Key Laboratory for Genome Stability and Human Disease Prevention, Department of Biochemistry and Molecular Biology, School of Medicine, Shenzhen University, Shenzhen 518060</wicri:regionArea><placeName><settlement type="city">Shenzhen</settlement><region type="province">Guangdong</region></placeName></affiliation></author></analytic><series><title level="j">Theranostics</title><idno type="eISSN">1838-7640</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p><bold>Background and Aim</bold>: DOT1L regulates various genes involved in cancer onset and progression by catalyzing H3K79 methylation, but how DOT1L activity itself is regulated is unclear. Here, we aimed to identify specific DOT1L post-translational modifications that might regulate DOT1L activity and thus impact on colorectal cancer (CRC) progression.</p><p><bold>Methods</bold>: We conducted affinity purification and mass spectrometry to explore DOT1L post-translational modifications. We then established transwell migration and invasion assays to specifically investigate the role of DOT1L(K358) acetylation on CRC cellular behavior <italic>in vitro</italic> and a bioluminescence imaging approach to determine the role of DOT1L(K358) acetylation in CRC metastasis <italic>in vivo</italic>. We performed chromatin immunoprecipitation to identify DOT1L acetylation-controlled target genes. Finally, we used immunohistochemical staining of human tissue arrays to examine the relevance of DOT1L(K358) acetylation in CRC progression and metastasis and the correlation between DOT1L acetylation and CBP.</p><p><bold>Results</bold>: We found that CBP mediates DOT1L K358 acetylation in human colon cancer cells and positively correlates with CRC stages. Mechanistically, DOT1L acetylation confers DOT1L stability by preventing the binding of RNF8 to DOT1L and subsequent proteasomal degradation, but does not affect its enzyme activity. Once stabilized, DOT1L can catalyze the H3K79 methylation of genes involved in epithelial-mesenchymal transition, including <italic>SNAIL</italic> and <italic>ZEB1</italic>. An acetylation mimic DOT1L mutant (Q358) could induce a cancer-like phenotype <italic>in vitro,</italic> characterized by metastasis and invasion. Finally, DOT1L(K358) acetylation correlated with CRC progression and a poor survival rate as well as with high CBP expression.</p><p><bold>Conclusions</bold>: DOT1L acetylation by CBP drives CRC progression and metastasis. 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uniqKey="Hou T" first="Tianyun" last="Hou">Tianyun Hou</name><name sortKey="Li, Meiting" sort="Li, Meiting" uniqKey="Li M" first="Meiting" last="Li">Meiting Li</name><name sortKey="Li, Yinglu" sort="Li, Yinglu" uniqKey="Li Y" first="Yinglu" last="Li">Yinglu Li</name><name sortKey="Li, Zhiming" sort="Li, Zhiming" uniqKey="Li Z" first="Zhiming" last="Li">Zhiming Li</name><name sortKey="Liu, Xiangyu" sort="Liu, Xiangyu" uniqKey="Liu X" first="Xiangyu" last="Liu">Xiangyu Liu</name><name sortKey="Lu, Xiaopeng" sort="Lu, Xiaopeng" uniqKey="Lu X" first="Xiaopeng" last="Lu">Xiaopeng Lu</name><name sortKey="Mao, Zebin" sort="Mao, Zebin" uniqKey="Mao Z" first="Zebin" last="Mao">Zebin Mao</name><name sortKey="Tang, Ming" sort="Tang, Ming" uniqKey="Tang M" first="Ming" last="Tang">Ming Tang</name><name sortKey="Wang, Haiying" sort="Wang, Haiying" uniqKey="Wang H" first="Haiying" last="Wang">Haiying Wang</name><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name><name sortKey="Wang, Hui" sort="Wang, Hui" uniqKey="Wang H" first="Hui" last="Wang">Hui Wang</name><name sortKey="Wen, He" sort="Wen, He" uniqKey="Wen H" first="He" last="Wen">He Wen</name><name sortKey="Yang, Qiaoyan" sort="Yang, Qiaoyan" uniqKey="Yang Q" first="Qiaoyan" last="Yang">Qiaoyan Yang</name><name sortKey="Yang, Yang" sort="Yang, Yang" uniqKey="Yang Y" first="Yang" last="Yang">Yang Yang</name><name sortKey="Zhao, Ying" sort="Zhao, Ying" uniqKey="Zhao Y" first="Ying" last="Zhao">Ying Zhao</name><name sortKey="Zhu, Qian" sort="Zhu, Qian" uniqKey="Zhu Q" first="Qian" last="Zhu">Qian Zhu</name><name sortKey="Zhu, Wei Guo" sort="Zhu, Wei Guo" uniqKey="Zhu W" first="Wei-Guo" last="Zhu">Wei-Guo Zhu</name><name sortKey="Zhu, Wei Guo" sort="Zhu, Wei Guo" uniqKey="Zhu W" first="Wei-Guo" last="Zhu">Wei-Guo Zhu</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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