The Insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in C. elegans
- The Hebrew University of Jerusalem, Israel
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.
Data availability
Mass Spectrometry data has been deposited at http://www.ebi.ac.uk/pride (Project accession: PXD010011).
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The Insulin/IGF Signaling Cascade Modulates SUMOylation to Regulate Aging and Proteostasis in C. elegansPRoteomics IDEntifications (PRIDE) database, PXD010011.
Article and author information
Author details
Funding
Israel Science Foundation (EC 981/16)
- Hana Boocholez
- Danielle Grushko
- Ehud Cohen
Israel Science Foundation (YBT 2090/15)
- Bar Lampert
- Yonatan B Tzur
Israel Science Foundation (YBT 1283/15)
- Bar Lampert
- Yonatan B Tzur
European Research Council (EC 281010)
- Lorna Moll
- Noa Roitenberg
- Michal Bejerano-Sagie
- Filipa Carvalhal Marques
- Yuli Volovik
- Tayir Elami
- Danielle Grushko
- Ehud Cohen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Inna Slutsky, Tel Aviv University, Israel
Version history
- Received: May 24, 2018
- Accepted: November 6, 2018
- Accepted Manuscript published: November 7, 2018 (version 1)
- Version of Record published: December 3, 2018 (version 2)
Copyright
© 2018, Moll et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The Insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in C. elegans
eLife 7:e38635.
https://doi.org/10.7554/eLife.38635
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