دورية أكاديمية
Wnt signaling modulates the response to DNA damage in the Drosophila wing imaginal disc by regulating the EGFR pathway.
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.) |
References: | Genes Dev. 1998 Feb 15;12(4):557-70. (PMID: 9472024) Dev Cell. 2011 Aug 16;21(2):366-74. (PMID: 21839923) Front Cell Dev Biol. 2022 Sep 06;10:993257. (PMID: 36147740) Nature. 1998 Jul 2;394(6688):82-4. (PMID: 9665132) Nat Methods. 2016 Oct;13(10):852-4. (PMID: 27595403) Cold Spring Harb Perspect Med. 2013 Oct 01;3(10):a014324. (PMID: 24086064) Dev Cell. 2005 Oct;9(4):463-75. (PMID: 16198289) Bioorg Chem. 2019 Jul;88:102925. (PMID: 31003078) Cell. 2017 Jun 1;169(6):985-999. (PMID: 28575679) Mol Cell Biol. 2004 Feb;24(3):1219-31. (PMID: 14729967) Development. 1993 Aug;118(4):1291-301. (PMID: 8269855) Mol Cell Biol. 2001 Oct;21(20):6768-81. (PMID: 11564862) EMBO J. 1999 Jun 1;18(11):3054-63. (PMID: 10357817) Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):E2967-76. (PMID: 25002478) Cell Death Discov. 2024 Jan 5;10(1):6. (PMID: 38182576) Elife. 2016 Feb 03;5:. (PMID: 26840050) Nat Med. 2018 Jul;24(7):939-946. (PMID: 29892062) Development. 2019 Aug 9;146(15):. (PMID: 31399474) Dev Cell. 2009 Jul;17(1):9-26. (PMID: 19619488) Cell Rep. 2019 Jul 2;28(1):119-131.e4. (PMID: 31269434) Nat Genet. 2006 Oct;38(10):1142-50. (PMID: 16980976) bioRxiv. 2024 Mar 14;:. (PMID: 38559130) Curr Biol. 2001 Jan 9;11(1):8-17. (PMID: 11166174) PLoS Genet. 2017 Oct 13;13(10):e1007055. (PMID: 29028797) Cell Death Differ. 2022 Apr;29(4):832-845. (PMID: 34824391) Curr Biol. 2004 Aug 10;14(15):1354-9. (PMID: 15296752) Genetics. 2018 Apr;208(4):1311-1336. (PMID: 29618590) Development. 2005 Sep;132(17):3935-46. (PMID: 16079158) Development. 2000 Aug;127(16):3619-29. (PMID: 10903185) Dev Cell. 2009 Jun;16(6):797-809. (PMID: 19531351) Mol Cell. 2001 May;7(5):915-26. (PMID: 11389839) PLoS Genet. 2008 Aug 08;4(8):e1000153. (PMID: 18688282) Am J Cancer Res. 2014 Dec 15;5(1):411-22. (PMID: 25628949) Nature. 2008 Sep 25;455(7212):552-6. (PMID: 18794899) Mol Cancer Res. 2017 Nov;15(11):1481-1490. (PMID: 28811361) Curr Biol. 2004 Aug 10;14(15):1341-7. (PMID: 15296750) Oncogene. 2004 May 27;23(25):4444-53. (PMID: 15064706) Cell. 2006 May 5;125(3):509-22. (PMID: 16678095) Dev Cell. 2020 Sep 14;54(5):583-592.e5. (PMID: 32888416) Genetics. 2005 Oct;171(2):845-7. (PMID: 16020777) PLoS Biol. 2018 Oct 31;16(10):e3000027. (PMID: 30379844) Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):7951-5. (PMID: 12048243) Development. 2014 Jan;141(1):112-23. (PMID: 24284207) DNA Repair (Amst). 2015 Aug;32:141-148. (PMID: 25957488) Cell. 2012 Jun 8;149(6):1192-205. (PMID: 22682243) Methods. 2014 Jun 15;68(1):89-96. (PMID: 24613678) Mol Cell. 2007 Dec 14;28(5):739-45. (PMID: 18082599) Genes Dev. 2004 Aug 1;18(15):1850-61. (PMID: 15256487) Mol Cell. 2010 Oct 22;40(2):179-204. (PMID: 20965415) Elife. 2020 Feb 13;9:. (PMID: 32053108) Cell. 1998 Oct 30;95(3):331-41. (PMID: 9814704) Mol Cell Biol. 2006 Oct;26(20):7601-15. (PMID: 16954388) Cell. 1998 Oct 30;95(3):319-29. (PMID: 9814703) Cell Physiol Biochem. 2018;48(2):419-432. (PMID: 30021193) Development. 2010 Apr;137(7):1169-79. (PMID: 20215351) PLoS Genet. 2018 Aug 24;14(8):e1007568. (PMID: 30142157) Cell Rep. 2020 Sep 8;32(10):108121. (PMID: 32905771) PLoS Biol. 2016 Sep 01;14(9):e1002536. (PMID: 27584613) Nat Commun. 2016 Mar 24;7:10994. (PMID: 27009971) |
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 |
تدمد: | 1545-7885 |
---|---|
DOI: | 10.1371/journal.pbio.3002547 |