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

Lei Pan, Su Wang, Tinglin Lu, Changjiang Weng, Xiaoqing Song, Joseph K. Park, Jin Sun, Zhi Hao Yang, Junjing Yu, Hong Tang, Dennis M. McKearin, Daniel A. Chamovitz, Jianquan Ni, Ting Xie*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)233-236
Number of pages4
Issue number7521
StatePublished - 9 Oct 2014


FundersFunder number
National Institutes of Health
National Institute of General Medical SciencesR01GM064428
Stowers Institute for Medical Research
National Natural Science Foundation of China31370909
Ministry of Science and Technology of the People's Republic of China2012CB518900


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