The insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in Caenorhabditis elegans

eLife

Lorna Moll¹  Ehud Cohen¹  Hana Boocholez¹  Michal Bejerano-Sagie¹  Filipa Carvalhal Marques¹  Danielle Grushko¹  Noa Roitenberg¹  Yuli Volovik¹  Tayir Elami¹  Atif Ahmed Siddiqui¹  Tommer Ravid²  Adi Biram²  Yonatan B Tzur³  Bar Lampert³  Hana Achache³ 

[1] 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;Departments of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel;

关键词: aging;    insulin/IGF signaling;    SUMOylation;    germline;    lifespan;    proteostasis;   

DOI  :  10.7554/eLife.38635

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown