ArticleOncogene2026
The RNA-binding protein RALY promotes ATM activation by stabilizing Tip60.
Bo Yao, Kailiang Zhao, Ning Yu, Ning Wang, Yinian Chang, Linzhu Luo, Fang Wang, Yide Mei
Abstract read
In one paragraphArticle in Oncogene, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
8 authors.
Bo YaoDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Kailiang ZhaoDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. zkailiang@ustc.edu.cn.ORCID http://orcid.org/0000-0001-8149-1494 Ning YuDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Ning WangDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Yinian ChangDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Linzhu LuoSchool of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Yide MeiDepartment of Thoracic Surgery, The First Affiliated Hospital of USTC, National Key Laboratory of Immune Response and Immunotherapy, Center for Advanced Interdisciplinary Science and Biomedicine of IHM, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. meiyide@ustc.edu.cn.ORCID http://orcid.org/0000-0002-8670-7394 Funding
National Natural Science Foundation of China (National Science Foundation of China) 32200614National Natural Science Foundation of China (National Science Foundation of China) 32270811National Natural Science Foundation of China (National Science Foundation of China) 32470749Natural Science Foundation of Anhui Province (Anhui Provincial Natural Science Foundation) 508085MH209
6 · The paper itselfAbstract
A rapid DNA damage response (DDR) and efficient DNA repair are essential for maintaining genome integrity. As a central apical kinase, ATM phosphorylates multiple downstream substrates to initiate DDR signaling and coordinate DNA repair following double-strand breaks (DSBs). However, the precise molecular mechanisms underlying ATM activation remain incompletely understood. Here, we identify the RNA-binding protein RALY as a critical regulator of ATM activation. We show that RALY directly interacts with and stabilizes the acetyltransferase Tip60, a key activator of ATM. Mechanistically, RALY competes with Tip60 for binding to the E3 ubiquitin ligase Mdm2, thereby inhibiting Mdm2-mediated ubiquitination and degradation of Tip60. Functionally, inhibition of RALY impairs ATM activation, compromises DNA repair capacity, and enhances radiosensitivity of cancer cells in a Tip60-dependent manner. Our findings uncover a previously unrecognized role of RALY in regulating ATM activation and indicate RALY as a potential therapeutic target for enhancing radiosensitivity in cancer.
Indexed as
Ataxia Telangiectasia Mutated ProteinsHistone AcetyltransferasesRNA-Binding ProteinsCell Line, TumorDNA Breaks, Double-StrandedDNA RepairHumansLysine Acetyltransferase 5PhosphorylationProto-Oncogene Proteins c-mdm2Radiation ToleranceUbiquitinationAtaxia Telangiectasia Mutated ProteinsATM protein, humanHistone AcetyltransferasesKAT5 protein, humanLysine Acetyltransferase 5MDM2 protein, humanProto-Oncogene Proteins c-mdm2RNA-Binding Proteins
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