دورية أكاديمية

Wnt signaling modulates the response to DNA damage in the Drosophila wing imaginal disc by regulating the EGFR pathway.

التفاصيل البيبلوغرافية
العنوان: Wnt signaling modulates the response to DNA damage in the Drosophila wing imaginal disc by regulating the EGFR pathway.
المؤلفون: Ewen-Campen B; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America., Perrimon N; Department of Genetics, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, United States of America.; Howard Hughes Medical Institute, Boston, Massachusetts, United States of America.
المصدر: PLoS biology [PLoS Biol] 2024 Jul 24; Vol. 22 (7), pp. e3002547. Date of Electronic Publication: 2024 Jul 24 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101183755 Publication Model: eCollection Cited Medium: Internet ISSN: 1545-7885 (Electronic) Linking ISSN: 15449173 NLM ISO Abbreviation: PLoS Biol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science, [2003]-
مواضيع طبية MeSH: ErbB Receptors*/metabolism , ErbB Receptors*/genetics , Drosophila Proteins*/metabolism , Drosophila Proteins*/genetics , Wings, Animal*/metabolism , Wings, Animal*/growth & development , Imaginal Discs*/metabolism , Imaginal Discs*/growth & development , Wnt1 Protein*/metabolism , Wnt1 Protein*/genetics , Wnt Signaling Pathway* , DNA Damage* , Apoptosis*/genetics, Animals ; Drosophila melanogaster/genetics ; Drosophila melanogaster/metabolism ; Drosophila melanogaster/growth & development ; Tumor Suppressor Protein p53/metabolism ; Tumor Suppressor Protein p53/genetics ; Checkpoint Kinase 2/metabolism ; Checkpoint Kinase 2/genetics ; Signal Transduction ; DNA Breaks, Double-Stranded ; Receptors, Invertebrate Peptide/metabolism ; Receptors, Invertebrate Peptide/genetics ; Drosophila/metabolism ; Drosophila/genetics ; Transcription Factors
مستخلص: Despite the deep conservation of the DNA damage response (DDR) pathway, cells in different contexts vary widely in their susceptibility to DNA damage and their propensity to undergo apoptosis as a result of genomic lesions. One of the cell signaling pathways implicated in modulating the DDR is the highly conserved Wnt pathway, which is known to promote resistance to DNA damage caused by ionizing radiation in a variety of human cancers. However, the mechanisms linking Wnt signal transduction to the DDR remain unclear. Here, we use a genetically encoded system in Drosophila to reliably induce consistent levels of DNA damage in vivo, and demonstrate that canonical Wnt signaling in the wing imaginal disc buffers cells against apoptosis in the face of DNA double-strand breaks. We show that Wg, the primary Wnt ligand in Drosophila, activates epidermal growth factor receptor (EGFR) signaling via the ligand-processing protease Rhomboid, which, in turn, modulates the DDR in a Chk2-, p53-, and E2F1-dependent manner. These studies provide mechanistic insight into the modulation of the DDR by the Wnt and EGFR pathways in vivo in a highly proliferative tissue. Furthermore, they reveal how the growth and patterning functions of Wnt signaling are coupled with prosurvival, antiapoptotic activities, thereby facilitating developmental robustness in the face of genomic damage.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Ewen-Campen, Perrimon. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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المشرفين على المادة: EC 2.7.10.1 (ErbB Receptors)
0 (Drosophila Proteins)
0 (Wnt1 Protein)
0 (wg protein, Drosophila)
0 (Tumor Suppressor Protein p53)
0 (E2f1 protein, Drosophila)
EC 2.7.10.1 (Egfr protein, Drosophila)
EC 2.7.1.11 (Checkpoint Kinase 2)
0 (p53 protein, Drosophila)
0 (Receptors, Invertebrate Peptide)
0 (Transcription Factors)
تواريخ الأحداث: Date Created: 20240724 Date Completed: 20240822 Latest Revision: 20240823
رمز التحديث: 20240823
DOI: 10.1371/journal.pbio.3002547
PMID: 39047051
قاعدة البيانات: MEDLINE
الوصف
تدمد:1545-7885
DOI:10.1371/journal.pbio.3002547