A Cyclin A-Myb-MuvB-Aurora B network regulates the choice between mitotic cycles and polyploid endoreplication cycles.
Autor: | Rotelli MD; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Policastro RA; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Bolling AM; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Killion AW; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Weinberg AJ; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Dixon MJ; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Zentner GE; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America., Walczak CE; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.; Indiana University School of Medicine, Bloomington, Indiana, United States of America., Lilly MA; National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America., Calvi BR; Department of Biology. Indiana University, Bloomington, Indiana, United States of America.; Melvin and Bren Simon Cancer Center, Indianapolis, Indiana, United States of America.; Indiana University School of Medicine, Bloomington, Indiana, United States of America. |
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Jazyk: | angličtina |
Zdroj: | PLoS genetics [PLoS Genet] 2019 Jul 10; Vol. 15 (7), pp. e1008253. Date of Electronic Publication: 2019 Jul 10 (Print Publication: 2019). |
DOI: | 10.1371/journal.pgen.1008253 |
Abstrakt: | Endoreplication is a cell cycle variant that entails cell growth and periodic genome duplication without cell division, and results in large, polyploid cells. Cells switch from mitotic cycles to endoreplication cycles during development, and also in response to conditional stimuli during wound healing, regeneration, aging, and cancer. In this study, we use integrated approaches in Drosophila to determine how mitotic cycles are remodeled into endoreplication cycles, and how similar this remodeling is between induced and developmental endoreplicating cells (iECs and devECs). Our evidence suggests that Cyclin A / CDK directly activates the Myb-MuvB (MMB) complex to induce transcription of a battery of genes required for mitosis, and that repression of CDK activity dampens this MMB mitotic transcriptome to promote endoreplication in both iECs and devECs. iECs and devECs differed, however, in that devECs had reduced expression of E2F1-dependent genes that function in S phase, whereas repression of the MMB transcriptome in iECs was sufficient to induce endoreplication without a reduction in S phase gene expression. Among the MMB regulated genes, knockdown of AurB protein and other subunits of the chromosomal passenger complex (CPC) induced endoreplication, as did knockdown of CPC-regulated cytokinetic, but not kinetochore, proteins. Together, our results indicate that the status of a CycA-Myb-MuvB-AurB network determines the decision to commit to mitosis or switch to endoreplication in both iECs and devECs, and suggest that regulation of different steps of this network may explain the known diversity of polyploid cycle types in development and disease. Competing Interests: The authors have declared that no competing interests exist. |
Databáze: | MEDLINE |
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