Stuxnet Facilitates the Degradation of Polycomb Protein during Development.
Stuxnet Facilitates the Degradation of Polycomb Protein during Development.
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Stuxnet 在开发过程中促进多梳蛋白的降解。
DOI：
10.1016/j.devcel.2016.05.013
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发表时间：
2016-06-20
影响因子：
11.8
通讯作者：
Zhu AJ
中科院分区：
文献类型：
--
作者：
Du J;Zhang J;He T;Li Y;Su Y;Tie F;Liu M;Harte PJ;Zhu AJ
多梳组（PcG）蛋白的功能，以确保正确部署的发展计划，通过表观遗传抑制靶基因的表达。尽管重要性，很少有研究集中在PcG活动本身的调节。在这里，我们报告了果蝇基因stuxnet（stx），控制Pc蛋白的稳定性。我们发现，stx活性升高导致同源异型转化，降低Pc活性和去阻遏的PcG目标。相反，stx突变体，这可以通过减少Pc表达获救，显示发育缺陷，类似于Pc的过度激活。我们的生化分析提供了机制的基础，stx和Pc之间的相互作用; Stx促进Pc降解的蛋白酶体独立的泛素修饰。此外，这种调节模式在脊椎动物中是保守的。在脊椎动物细胞中，小鼠stx促进Cbx 4（一种正向的Pc蛋白）的降解，并在果蝇中诱导同源异型转化。我们的研究结果强调了一个进化上保守的机制，调节蛋白质降解PcG稳态和表观遗传活性。多梳组蛋白（Polycomb-group，PcG）是一种保守的表观遗传发育调控因子。Du等人表明，Stuxnet蛋白是Polycomb稳态和PcG活性的保守调节因子。Stuxnet依赖于一个泛素样结构域，绕过泛素化步骤，直接靶向Polycomb蛋白进行蛋白酶体降解。
Polycomb-group (PcG) proteins function to ensure correct deployment of developmental programs by epigenetically repressing target gene expression. Despite the importance, few studies have been focused on the regulation of PcG activity itself. Here, we report a Drosophila gene stuxnet (stx) that controls Pc protein stability. We find that heightened stx activity leads to homeotic transformation, reduced Pc activity and de-repression of PcG targets. Conversely, stx mutants, which can be rescued by decreased Pc expression, display developmental defects resembling hyper-activation of Pc. Our biochemical analyses provide mechanistic basis for the interaction between stx and Pc; Stx facilitates Pc degradation in the proteasome independent of ubiquitin modification. Furthermore, this mode of regulation is conserved in vertebrates. Mouse stx promotes degradation of Cbx4, an orthologous Pc protein, in vertebrate cells, and induces homeotic transformation in Drosophila. Our results highlight an evolutionarily conserved mechanism of regulated protein degradation on PcG homeostasis and epigenetic activity. Polycomb-group (PcG) proteins are conserved epigenetic regulators of development. Du et al. show that the Stuxnet protein is a conserved regulator of Polycomb homeostasis and PcG activity. Stuxnet relies on a ubiquitin-like domain, bypassing a ubiquitination step, to directly target Polycomb proteins for proteasomal degradation.
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影响因子：
14.9
作者：
Contrino S;Smith RN;Butano D;Carr A;Hu F;Lyne R;Rutherford K;Kalderimis A;Sullivan J;Carbon S;Kephart ET;Lloyd P;Stinson EO;Washington NL;Perry MD;Ruzanov P;Zha Z;Lewis SE;Stein LD;Micklem G
通讯作者：
Micklem G
影响因子：
7.8
作者：
Buchenau, P;Hodgson, J;Strutt, H;Arndt-Jovin, DJ
通讯作者：
Arndt-Jovin, DJ
影响因子：
1.6
作者：
Dietzel, S;Niemann, H;Paro, R
通讯作者：
Paro, R
影响因子：
10.5
作者：
FAUVARQUE, MO;DURA, JM
通讯作者：
DURA, JM
影响因子：
5.3
作者：
Ali, JY;Bender, W
通讯作者：
Bender, W