TY - JOUR TI - The insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in Caenorhabditis elegans AU - Moll, Lorna AU - Roitenberg, Noa AU - Bejerano-Sagie, Michal AU - Boocholez, Hana AU - Carvalhal Marques, Filipa AU - Volovik, Yuli AU - Elami, Tayir AU - Siddiqui, Atif Ahmed AU - Grushko, Danielle AU - Biram, Adi AU - Lampert, Bar AU - Achache, Hana AU - Ravid, Tommer AU - Tzur, Yonatan B AU - Cohen, Ehud A2 - Slutsky, Inna A2 - VijayRaghavan, K VL - 7 PY - 2018 DA - 2018/11/07 SP - e38635 C1 - eLife 2018;7:e38635 DO - 10.7554/eLife.38635 UR - https://doi.org/10.7554/eLife.38635 AB - 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 Caenorhabditis elegans 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 glp-1. 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. KW - aging KW - insulin/IGF signaling KW - SUMOylation KW - germline KW - lifespan KW - proteostasis JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -