دورية أكاديمية
أعرض في EDS

SOD1 is a synthetic-lethal target in PPM1D -mutant leukemia cells.

التفاصيل البيبلوغرافية
العنوان: SOD1 is a synthetic-lethal target in PPM1D -mutant leukemia cells.
المؤلفون: Zhang L; Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, United States.; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States., Hsu JI; Translational Biology and Molecular Medicine Graduate Program, Baylor College of Medicine, Houston, United States.; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States., Braekeleer ED; Department of Haematology, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom., Chen CW; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.; Integrated Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, United States., Patel TD; Texas Children's Hospital Department of Hematology/Oncology, Baylor College of Medicine, Houston, United States., Martell AG; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States., Guzman AG; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States., Wohlan K; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States., Waldvogel SM; Medical Scientist Training Program, Baylor College of Medicine, Houston, United States.; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.; Cancer and Cell Biology Graduate Program, Baylor College of Medicine, Houston, United States., Uryu H; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, United States., Tovy A; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States., Callen E; Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, Bethesda, United States., Murdaugh RL; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.; Department of Neurosurgery, Baylor College of Medicine, Houston, United States., Richard R; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.; Department of Neurosurgery, Baylor College of Medicine, Houston, United States., Jansen S; Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands., Vissers L; Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands., de Vries BBA; Donders Centre for Neuroscience, Radboud University Medical Center, Nijmegen, Netherlands., Nussenzweig A; Laboratory of Genome Integrity, National Cancer Institute, National Institute of Health, Bethesda, United States., Huang S; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Department of Education, Innovation and Technology, Advanced Technology Cores, University of Texas, Houston, United States., Coarfa C; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States., Anastas J; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.; Department of Neurosurgery, Baylor College of Medicine, Houston, United States., Takahashi K; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, United States.; Department of Genome Medicine, The University of Texas MD Anderson Cancer Center, Houston, United States., Vassiliou G; Department of Haematology, Wellcome-MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom., Goodell MA; Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, United States.; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, United States.; Center for Cell and Gene Therapy, Houston, United States.
المصدر: ELife [Elife] 2024 Jun 18; Vol. 12. Date of Electronic Publication: 2024 Jun 18.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Protein Phosphatase 2C*/metabolism , Protein Phosphatase 2C*/genetics , Superoxide Dismutase-1*/genetics , Superoxide Dismutase-1*/metabolism, Humans ; Cell Line, Tumor ; Leukemia/genetics ; CRISPR-Cas Systems ; Oxidative Stress ; Reactive Oxygen Species/metabolism ; Synthetic Lethal Mutations ; Mutation
مستخلص: The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase Mg 2+ /Mn 2+ -dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacological target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D -mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D -mutant cells. Altogether, our results demonstrate a role for SOD1 in the survival of PPM1D -mutant leukemia cells and highlight a new potential therapeutic strategy against PPM1D -mutant cancers.
Competing Interests: LZ, JH, EB, CC, TP, AM, AG, KW, SW, HU, AT, EC, RM, RR, SJ, LV, Bd, AN, SH, CC, JA, KT, GV, MG No competing interests declared
التعليقات: Update of: bioRxiv. 2024 Jan 17:2023.08.31.555634. doi: 10.1101/2023.08.31.555634. (PMID: 37693622)
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معلومات مُعتمدة: F30 DK116428 United States DK NIDDK NIH HHS; F30HD111129 Eunice Kennedy Shriver National Institute of Child Health & Human Development; Scholar Award Leukemia and Lymphoma Society; P30 CA125123 United States CA NCI NIH HHS; F30DK116428 United States DK NIDDK NIH HHS; R01 CA237291 United States CA NCI NIH HHS; F30 HD111129 United States HD NICHD NIH HHS; S10 RR024574 United States RR NCRR NIH HHS; P01CA265748 United States CA NCI NIH HHS; S10 OD028648 United States OD NIH HHS; P01 CA265748 United States CA NCI NIH HHS; P30CA125123 United States CA NCI NIH HHS; R01CA237291 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: DNA damage; cancer; cancer biology; cell biology; leukemia; mouse
سلسلة جزيئية: GEO GSE240874
المشرفين على المادة: EC 3.1.3.16 (Protein Phosphatase 2C)
EC 3.1.3.16 (PPM1D protein, human)
EC 1.15.1.1 (Superoxide Dismutase-1)
0 (SOD1 protein, human)
0 (Reactive Oxygen Species)
تواريخ الأحداث: Date Created: 20240619 Date Completed: 20240619 Latest Revision: 20240628
رمز التحديث: 20240629
مُعرف محوري في PubMed: PMC11186636
DOI: 10.7554/eLife.91611
PMID: 38896450
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.91611