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Rewired m6A epitran...
Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation
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- Xu, An (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Liu, Mo (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Huang, Mo-Fan (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States; University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, TX, Houston, United States
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- Zhang, Yang (författare)
- College of Science, Harbin Institute of Technology (Shenzhen), Guangdong, Shenzhen, China
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- Hu, Ruifeng (författare)
- Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Gingold, Julian A. (författare)
- Department of Obstetrics & Gynecology and Women's Health, Einstein/Montefiore Medical Center, NY, Bronx, United States
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- Liu, Ying (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Zhu, Dandan (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Chien, Chian-Shiu (författare)
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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- Wang, Wei-Chen (författare)
- Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan
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- Liao, Zian (författare)
- Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, TX, Houston, United States
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- Yuan, Fei (författare)
- Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, TX, Houston, United States
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- Hsu, Chih-Wei (författare)
- Department of Molecular Physiology and Biophysics, Baylor College of Medicine, TX, Houston, United States
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- Tu, Jian (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Yu, Yao (författare)
- Department of Epidemiology, University of Texas MD Anderson Cancer Center, TX, Houston, United States
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- Rosen, Taylor (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Xiong, Feng (författare)
- Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Jia, Peilin (författare)
- Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Yang, Yi-Ping (författare)
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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- Bazer, Danielle A. (författare)
- Department of Neurology, Renaissance School of Medicine at Stony Brook University, Stony Brook, NY, United States
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- Chen, Ya-Wen (författare)
- Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Department of Cell, Developmental and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Black Family Stem Cell Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA; Institute for Airway Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
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- Li, Wenbo (författare)
- University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, TX, Houston, United States; Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Huff, Chad D. (författare)
- University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, TX, Houston, United States; Department of Epidemiology, University of Texas MD Anderson Cancer Center, TX, Houston, United States
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- Zhu, Jay-Jiguang (författare)
- Department of Neurosurgery, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Aguilo, Francesca, PhD (författare)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Institutionen för molekylärbiologi (Medicinska fakulteten)
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- Chiou, Shih-Hwa (författare)
- Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
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- Boles, Nathan C. (författare)
- Neural Stem Cell Institute, NY, Rensselaer, United States
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- Lai, Chien-Chen (författare)
- Institute of Molecular Biology, National Chung Hsing University, Taichung, Taiwan; Graduate institute of Chinese Medical Science, China Medical University, Taichung, Taiwan; Ph.D. Program in Translational Medicine and Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung, Taiwan
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- Hung, Mien-Chie (författare)
- Graduate Institute of Biomedical Sciences and Center for Molecular Medicine, Office of the President, China Medical University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan
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- Zhao, Zhongming (författare)
- University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, TX, Houston, United States; Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Van Nostrand, Eric L. (författare)
- Verna & Marrs McLean Department of Biochemistry & Molecular Biology and Therapeutic Innovation Center, Baylor College of Medicine, TX, Houston, United States
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- Zhao, Ruiying (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States
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- Lee, Dung-Fang (författare)
- Department of Integrative Biology and Pharmacology, McGovern Medical School, University of Texas Health Science Center at Houston, TX, Houston, United States; University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences, TX, Houston, United States; Center for Precision Health, School of Biomedical Informatics, University of Texas Health Science Center at Houston, TX, Houston, United States; Center for Stem Cell and Regenerative Medicine, Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, University of Texas Health Science Center at Houston, TX, Houston, United States
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(creator_code:org_t)
- 2023-03-27
- 2023
- Engelska.
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
- Relaterad länk:
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https://doi.org/10.1...
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https://umu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- N6-methyladenosine (m6A), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of m6A epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas. We find that mutant p53 but not wild-type (WT) p53 physically interacts with SVIL to recruit the H3K4me3 methyltransferase MLL1 to activate the expression of m6A reader YTHDF2, culminating in an oncogenic phenotype. Aberrant YTHDF2 upregulation markedly hampers expression of multiple m6A-marked tumor-suppressing transcripts, including CDKN2B and SPOCK2, and induces oncogenic reprogramming. Mutant p53 neoplastic behaviors are significantly impaired by genetic depletion of YTHDF2 or by pharmacological inhibition using MLL1 complex inhibitors. Our study reveals how mutant p53 hijacks epigenetic and epitranscriptomic machinery to initiate gliomagenesis and suggests potential treatment strategies for LFS gliomas.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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Till lärosätets databas
- Av författaren/redakt...
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Xu, An
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Liu, Mo
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Huang, Mo-Fan
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Zhang, Yang
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Hu, Ruifeng
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Gingold, Julian ...
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visa fler...
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Liu, Ying
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Zhu, Dandan
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Chien, Chian-Shi ...
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Wang, Wei-Chen
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Liao, Zian
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Yuan, Fei
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Hsu, Chih-Wei
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Tu, Jian
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Yu, Yao
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Rosen, Taylor
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Xiong, Feng
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Jia, Peilin
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Yang, Yi-Ping
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Bazer, Danielle ...
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Chen, Ya-Wen
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Li, Wenbo
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Huff, Chad D.
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Zhu, Jay-Jiguang
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Aguilo, Francesc ...
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Chiou, Shih-Hwa
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Boles, Nathan C.
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Lai, Chien-Chen
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Hung, Mien-Chie
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Zhao, Zhongming
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Van Nostrand, Er ...
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Zhao, Ruiying
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Lee, Dung-Fang
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