Department of Biochemistry and Molecular Biology, Institute for Medical Research Israel-Canada, The Hebrew University School of Medicine, Jerusalem, Israel.
Departments of Biological Chemistry, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Elife. 2018 Nov 7;7:e38635. doi: 10.7554/eLife.38635.
Although aging-regulating pathways were discovered a few decades ago, it is not entirely clear how their activities are orchestrated, to govern lifespan and proteostasis at the organismal level. Here, we utilized the nematode to examine whether the alteration of aging, by reducing the activity of the Insulin/IGF signaling (IIS) cascade, affects protein SUMOylation. We found that IIS activity promotes the SUMOylation of the germline protein, CAR-1, thereby shortening lifespan and impairing proteostasis. In contrast, the expression of mutated CAR-1, that cannot be SUMOylated at residue 185, extends lifespan and enhances proteostasis. A mechanistic analysis indicated that CAR-1 mediates its aging-altering functions, at least partially, through the notch-like receptor . Our findings unveil a novel regulatory axis in which SUMOylation is utilized to integrate the aging-controlling functions of the IIS and of the germline and provide new insights into the roles of SUMOylation in the regulation of organismal aging.
尽管衰老调节途径在几十年前就被发现了，但它们的活动如何协调以在机体水平上控制寿命和蛋白质稳态还不完全清楚。在这里，我们利用线虫来研究通过降低胰岛素/胰岛素样生长因子信号（IIS）级联的活性来改变衰老是否会影响蛋白质 SUMO 化。我们发现，IIS 活性促进生殖系蛋白 CAR-1 的 SUMO 化，从而缩短寿命并损害蛋白质稳态。相比之下，不能在残基 185 处被 SUMO 化的突变型 CAR-1 的表达延长了寿命并增强了蛋白质稳态。机制分析表明，CAR-1 通过 Notch 样受体介导其改变衰老的功能，至少部分是这样。我们的发现揭示了一个新的调节轴，其中 SUMO 化被用来整合 IIS 和生殖系的衰老控制功能，并为 SUMO 化在调节机体衰老中的作用提供了新的见解。
