دورية أكاديمية

Phosphoproteomics of ATR signaling in mouse testes.

التفاصيل البيبلوغرافية
العنوان: Phosphoproteomics of ATR signaling in mouse testes.
المؤلفون: Sims JR; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States., Faça VM; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.; Department of Biochemistry and Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil., Pereira C; Department of Biomedical Sciences, Cornell University, Ithaca, United States., Ascenção C; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States., Comstock W; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States., Badar J; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States., Arroyo-Martinez GA; Department of Biomedical Sciences, Cornell University, Ithaca, United States., Freire R; Unidad de Investigación, Hospital Universitario de Canarias, Tenerife, Spain.; Instituto de Tecnologías Biomédicas, Universidad de La Laguna, La Laguna, Spain.; Universidad Fernando Pessoa Canarias, Las Palmas de Gran Canaria, Spain., Cohen PE; Department of Biomedical Sciences, Cornell University, Ithaca, United States., Weiss RS; Department of Biomedical Sciences, Cornell University, Ithaca, United States., Smolka MB; Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, United States.
المصدر: ELife [Elife] 2022 Feb 08; Vol. 11. Date of Electronic Publication: 2022 Feb 08.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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: Proteome*, Ataxia Telangiectasia Mutated Proteins/*metabolism , Testis/*metabolism, Animals ; Ataxia Telangiectasia Mutated Proteins/genetics ; DNA Damage ; DNA Repair ; Male ; Meiosis ; Mice, Inbred C57BL ; Morpholines/administration & dosage ; Phosphorylation ; Pyrimidines/administration & dosage ; RNA, Messenger/metabolism ; Signal Transduction ; Spermatocytes/metabolism ; Mice
مستخلص: The phosphatidylinositol 3' kinase (PI3K)-related kinase ATR is crucial for mammalian meiosis. ATR promotes meiotic progression by coordinating key events in DNA repair, meiotic sex chromosome inactivation (MSCI), and checkpoint-dependent quality control during meiotic prophase I. Despite its central roles in meiosis, the ATR-dependent meiotic signaling network remains largely unknown. Here, we used phosphoproteomics to define ATR signaling events in testes from mice following chemical and genetic ablation of ATR signaling. Quantitative analysis of phosphoproteomes obtained after germ cell-specific genetic ablation of the ATR activating 9-1-1 complex or treatment with ATR inhibitor identified over 14,000 phosphorylation sites from testes samples, of which 401 phosphorylation sites were found to be dependent on both the 9-1-1 complex and ATR. Our analyses identified ATR-dependent phosphorylation events in crucial DNA damage signaling and DNA repair proteins including TOPBP1, SMC3, MDC1, RAD50, and SLX4. Importantly, we identified ATR and RAD1-dependent phosphorylation events in proteins involved in mRNA regulatory processes, including SETX and RANBP3, whose localization to the sex body was lost upon ATR inhibition. In addition to identifying the expected ATR-targeted S/T-Q motif, we identified enrichment of an S/T-P-X-K motif in the set of ATR-dependent events, suggesting that ATR promotes signaling via proline-directed kinase(s) during meiosis. Indeed, we found that ATR signaling is important for the proper localization of CDK2 in spermatocytes. Overall, our analysis establishes a map of ATR signaling in mouse testes and highlights potential meiotic-specific actions of ATR during prophase I progression.
Competing Interests: JS, VF, CP, CA, WC, JB, GA, RF, PC, RW, MS No competing interests declared
(© 2022, Sims et al.)
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معلومات مُعتمدة: R01 HD041012 United States HD NICHD NIH HHS; R01 HD095296 United States HD NICHD NIH HHS; R01 HD097987 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: 9-1-1; ATR; biochemistry; chemical biology; developmental biology; meiosis; mouse; prophase I; sex body
المشرفين على المادة: 0 (4-(4-(3-methylmorpholin-4-yl)-6-(1-(methylsulfonyl)cyclopropyl)pyrimidin-2-yl)-1H-indole)
0 (Morpholines)
0 (Proteome)
0 (Pyrimidines)
0 (RNA, Messenger)
EC 2.7.11.1 (Ataxia Telangiectasia Mutated Proteins)
تواريخ الأحداث: Date Created: 20220208 Date Completed: 20220222 Latest Revision: 20240226
رمز التحديث: 20240226
مُعرف محوري في PubMed: PMC8824463
DOI: 10.7554/eLife.68648
PMID: 35133275
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.68648