Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development.
Coupled Caspase and N-End Rule Ligase Activities Allow Recognition and Degradation of Pluripotency Factor LIN-28 during Non-Apoptotic Development.
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DOI：
10.1016/j.devcel.2017.05.013
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发表时间：
2017-06-19
影响因子：
11.8
通讯作者：
Han M
中科院分区：
文献类型：
--
作者：
Weaver BP;Weaver YM;Mitani S;Han M
最近的研究结果表明，经典的细胞死亡机制的组成部分也有重要的非细胞死亡（非凋亡）的功能，在苍蝇，线虫，和哺乳动物。然而，非典型的caspase底物识别和蛋白水解的机制，以及caspase在基因表达调控中的直接作用仍然很不清楚。在这里，我们报告了CED-3半胱天冬酶和Arg/N末端规则途径合作灭活缝细胞（C中的一种干细胞样细胞类型）中的LIN-28多能性因子。elegans，从而确保适当的时间细胞命运模式。重要的是，胱天蛋白酶和E3连接酶以非加和的方式执行该功能。我们表明，CED-3半胱天冬酶和E3泛素连接酶UBR-1形成一个复合物，耦合其在体内的活动，允许识别和快速降解的LIN-28，从而促进开关的发展计划。这些蛋白水解活性的相互依赖性为非凋亡半胱天冬酶介导的蛋白质失活提供了范例。胱天蛋白酶CED-3在C.优雅Weaver等人表明，CED-3的这种非凋亡功能与Arg/N-末端规则途径的泛素连接酶协同发生，并且这两种蛋白质的活性都是LIN-28的有效识别和降解所需的。
Recent findings suggest that components of the classical cell death machinery also have important non-cell death (non-apoptotic) functions in flies, nematodes, and mammals. However, the mechanisms for non-canonical caspase substrate recognition and proteolysis, and direct roles for caspases in gene expression regulation remain largely unclear. Here we report that CED-3 caspase and the Arg/N-end rule pathway cooperate to inactivate the LIN-28 pluripotency factor in seam cells, a stem-like cell type in C. elegans, thereby ensuring proper temporal cell fate patterning. Importantly, the caspase and the E3 ligase execute this function in a non-additive manner. We show that CED-3 caspase and the E3 ubiquitin ligase UBR-1 form a complex that couples their in vivo activities, allowing for recognition and rapid degradation of LIN-28, and thus facilitating a switch in developmental programs. The inter-dependence of these proteolytic activities provides a paradigm for non-apoptotic caspase-mediated protein inactivation. The caspase CED-3 cleaves the LIN-28 protein to limit its activity during seam cell patterning in C. elegans. Weaver et al. show that this non-apoptotic function of CED-3 occurs in collaboration with a ubiquitin ligase of the Arg/N-end rule pathway, and that activities of both of these proteins are required for efficient recognition and degradation of LIN-28.
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影响因子：
14.9
作者：
Mitchell A;Chang HY;Daugherty L;Fraser M;Hunter S;Lopez R;McAnulla C;McMenamin C;Nuka G;Pesseat S;Sangrador-Vegas A;Scheremetjew M;Rato C;Yong SY;Bateman A;Punta M;Attwood TK;Sigrist CJ;Redaschi N;Rivoire C;Xenarios I;Kahn D;Guyot D;Bork P;Letunic I;Gough J;Oates M;Haft D;Huang H;Natale DA;Wu CH;Orengo C;Sillitoe I;Mi H;Thomas PD;Finn RD
通讯作者：
Finn RD
影响因子：
2.5
作者：
Joshi, Pradeep M.;Riddle, Misty R.;Djabrayan, Nareg J. V.;Rothman, Joel H.
通讯作者：
Rothman, Joel H.
影响因子：
56.9
作者：
AMBROS, V;HORVITZ, HR
通讯作者：
HORVITZ, HR
影响因子：
14.9
作者：
UniProt Consortium
通讯作者：
UniProt Consortium
影响因子：
16.8
作者：
Prakash, S;Tian, L;Matouschek, A
通讯作者：
Matouschek, A