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

机译：蛋白质竞争将COP9的功能从自我更新转换为分化

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摘要

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.
机译：干细胞自我更新与分化之间的平衡受内在因素和利基信号的控制。在果蝇卵巢中，一些内在因素促进种系干细胞（GSC）的自我更新，而其他则刺激分化。然而，人们对如何控制自我更新与差异之间的平衡仍然知之甚少。在这里，我们使用D. melanogoaster卵巢GSCs来证明分化因子Bam控制COP9复合物的功能转换，即通过蛋白质竞争从自我更新到分化。 COP9复合物由八个Csn亚基Csn1-8组成，并从靶蛋白中去除Nedd8修饰。遗传结果表明，COP9复合物是GSC自我更新的内在必需，而其他Csn蛋白（Csn4除外）也是GSC后代分化所必需的。通过蛋白质竞争从COP9复合物中隔离Bam介导的Csn4，从而使COP9的自我更新功能失活，并允许其他Csn蛋白促进GSC分化。因此，这项研究揭示了一种基于蛋白质竞争的机制来控制干细胞自我更新与分化之间的平衡。因为在各种系统的整个干细胞谱系中无处不在表达大量的自我更新因子，所以蛋白质竞争可能是控制自我更新-分化转换的重要机制。

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  • 来源
    《Nature》 |2014年第7521期|233-236|共4页
  • 作者

    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;

  • 作者单位

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA,Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China;

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA,Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA;

    Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA;

    Department of Molecular Biology and Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA,Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA;

    Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

    Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA,Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China;

    Chinese Academy of Sciences Key Laboratory of Infection and Immunity, Institute of Biophysics, 15 Da Tun Road, Beijing 100101, China;

    Department of Molecular Biology and Graduate School of Biomedical Sciences, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9148, USA,Howard Hughes Medical Institute, Chevy Chase, Maryland 20815-6789, USA;

    Department of Plant Sciences, Tel Aviv University, Tel Aviv 69978, Israel;

    Center for Life Sciences, School of Medicine, Tsinghua University, Beijing 100084, China;

    Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA,Department of Cell Biology and Anatomy, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, Kansas 66160, USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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