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Pan, L., Wang, S., Lu, T., Weng, C., Song, X., Park, J.K., Sun, J., Yang, Z.H., Yu, J., Tang, H., McKearin, D.M., Chamovitz, D.A., Ni, J., Xie, T. (2014). Protein competition switches the function of COP9 from self-renewal to differentiation.  Nature 514(7521): 233--236.
FlyBase ID
FBrf0226469
Publication Type
Research paper
Abstract

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.

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Related Publication(s)
Note

A competitive cell fate switch.
Carreira-Rosario and Buszczak, 2014, Dev. Cell 31(3): 261--262 [FBrf0226904]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nature
    Title
    Nature
    Publication Year
    1869-
    ISBN/ISSN
    0028-0836
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