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Protein competition switches the function of COP9 from self-renewal to differentiation

doi: 10.1038/nature13562
pmid: 25119050
Protein competition switches the function of COP9 from self-renewal to differentiation
The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation. However, it remains poorly understood how the balance between self-renewal and differentiation is controlled. Here we use D. melanogaster ovarian GSCs to demonstrate that the differentiation factor Bam controls the functional switch of the COP9 complex from self-renewal to differentiation via protein competition. The COP9 complex is composed of eight Csn subunits, Csn1-8, and removes Nedd8 modifications from target proteins. Genetic results indicated that the COP9 complex is required intrinsically for GSC self-renewal, whereas other Csn proteins, with the exception of Csn4, were also required for GSC progeny differentiation. Bam-mediated Csn4 sequestration from the COP9 complex via protein competition inactivated the self-renewing function of COP9 and allowed other Csn proteins to promote GSC differentiation. Therefore, this study reveals a protein-competition-based mechanism for controlling the balance between stem cell self-renewal and differentiation. Because numerous self-renewal factors are ubiquitously expressed throughout the stem cell lineage in various systems, protein competition may function as an important mechanism for controlling the self-renewal-to-differentiation switch.
- Tsinghua University China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- University of Kansas United States
- Tel Aviv University Israel
- Hong Kong University of Science and Technology (香港科技大學) China (People's Republic of)
Male, NEDD8 Protein, COP9 Signalosome Complex, Stem Cells, Ovary, DNA Helicases, Intracellular Signaling Peptides and Proteins, Cell Differentiation, Binding, Competitive, Drosophila melanogaster, Multiprotein Complexes, Animals, Drosophila Proteins, Female, Ubiquitins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Peptide Hydrolases, Protein Binding
Male, NEDD8 Protein, COP9 Signalosome Complex, Stem Cells, Ovary, DNA Helicases, Intracellular Signaling Peptides and Proteins, Cell Differentiation, Binding, Competitive, Drosophila melanogaster, Multiprotein Complexes, Animals, Drosophila Proteins, Female, Ubiquitins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Peptide Hydrolases, Protein Binding
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