| Cyclin E controls Drosophila female germline stem cell maintenance independently of its role in proliferation by modulating responsiveness to niche signals. | |
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MedLine Citation:
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PMID: 23293285 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Stem cells must proliferate while maintaining 'stemness'; however, much remains to be learned about how factors that control the division of stem cells influence their identity. Multiple stem cell types display cell cycles with short G1 phases, thought to minimize susceptibility to differentiation factors. Drosophila female germline stem cells (GSCs) have short G1 and long G2 phases, and diet-dependent systemic factors often modulate G2. We previously observed that Cyclin E (CycE), a known G1/S regulator, is atypically expressed in GSCs during G2/M; however, it remained unclear whether CycE has cell cycle-independent roles in GSCs or whether it acts exclusively by modulating the cell cycle. In this study, we detected CycE activity during G2/M, reflecting its altered expression pattern, and showed that CycE and its canonical partner, Cyclin-dependent kinase 2 (Cdk2), are required not only for GSC proliferation, but also for GSC maintenance. In genetic mosaics, CycE- and Cdk2-deficient GSCs are rapidly lost from the niche, remain arrested in a G1-like state, and undergo excessive growth and incomplete differentiation. However, we found that CycE controls GSC maintenance independently of its role in the cell cycle; GSCs harboring specific hypomorphic CycE mutations are not efficiently maintained despite normal proliferation rates. Finally, CycE-deficient GSCs have an impaired response to niche bone morphogenetic protein signals that are required for GSC self-renewal, suggesting that CycE modulates niche-GSC communication. Taken together, these results show unequivocally that the roles of CycE/Cdk2 in GSC division cycle regulation and GSC maintenance are separable, and thus potentially involve distinct sets of phosphorylation targets. |
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Authors:
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Elizabeth T Ables; Daniela Drummond-Barbosa |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Development (Cambridge, England) Volume: 140 ISSN: 1477-9129 ISO Abbreviation: Development Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-07 Completed Date: 2013-03-07 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8701744 Medline TA: Development Country: England |
Other Details:
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Languages: eng Pagination: 530-40 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Animals Apoptosis Cell Division Cell Proliferation* Cyclin B / genetics, metabolism Cyclin E / genetics, metabolism* Cyclin-Dependent Kinase 2 / genetics, metabolism Drosophila / cytology*, metabolism Drosophila Proteins / genetics, metabolism Female G2 Phase Germ Cells / cytology, metabolism Green Fluorescent Proteins / metabolism Intercellular Junctions / genetics, metabolism Mutation Phenotype Signal Transduction Stem Cell Niche* Stem Cells / cytology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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F32 GM086031/GM/NIGMS NIH HHS; GM069875/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CycB protein, Drosophila; 0/Cyclin B; 0/Cyclin E; 0/Drosophila Proteins; 147336-22-9/Green Fluorescent Proteins; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/cdc2c protein, Drosophila |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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