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

Lorna Moll, Noa Roitenberg, Michal Bejerano-Sagie, Hana Boocholez, Filipa Carvalhal Marques, Yuli Volovik, Tayir Elami, Atif Ahmed Siddiqui, Danielle Grushko, Adi Biram, Bar Lampert, Hana Achache, Tommer Ravid, Yonatan B. Tzur, Ehud Cohen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

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.

Original languageAmerican English
Article numbere38635
JournaleLife
Volume7
DOIs
StatePublished - 1 Nov 2018

Bibliographical note

Publisher Copyright:
© Moll et al.

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