Protein competition switches the function of COP9 from self-renewal to differentiation，Nature, Published online 06 August 2014
发布时间：2014年08月07日
Nature, Received 07 November 2013，Accepted 06 June 2014，Published online 06 August 2014, doi:10.1038/nature13562
Protein competition switches the function of COP9 from self-renewal to differentiation
Lei Pan,1, 2, 8, Su Wang,1, 3, 8, Tinglin Lu,4, 8, Changjiang Weng,1, Xiaoqing Song,1, Joseph K. Park,5, 6, Jin Sun,4, Zhi-Hao Yang,4, Junjing Yu,1, 2, Hong Tang,2, Dennis M. McKearin,5, 6, Daniel A. Chamovitz,7, Jianquan Ni4, & Ting Xie1, 3,
Abstract
The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals1, 2. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation3. 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 proteins4, 5. 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.
附件下载：
Protein competition switches the function of COP9 from self-renewal to differentiation，Nature, Published online 06 August 2014
Nature, Received 07 November 2013，Accepted 06 June 2014，Published online 06 August 2014, doi:10.1038/nature13562
Protein competition switches the function of COP9 from self-renewal to differentiation
Lei Pan,1, 2, 8, Su Wang,1, 3, 8, Tinglin Lu,4, 8, Changjiang Weng,1, Xiaoqing Song,1, Joseph K. Park,5, 6, Jin Sun,4, Zhi-Hao Yang,4, Junjing Yu,1, 2, Hong Tang,2, Dennis M. McKearin,5, 6, Daniel A. Chamovitz,7, Jianquan Ni4, & Ting Xie1, 3,
Abstract
The balance between stem cell self-renewal and differentiation is controlled by intrinsic factors and niche signals1, 2. In the Drosophila melanogaster ovary, some intrinsic factors promote germline stem cell (GSC) self-renewal, whereas others stimulate differentiation3. 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 proteins4, 5. 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.
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201408/t20140807_4172001.html
文章链接：http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13562.html