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The Insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in C. elegans

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Cite this article as: eLife 2018;7:e38635 doi: 10.7554/eLife.38635

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.

Article and author information

Author details

  1. Lorna Moll

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  2. Noa Roitenberg

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  3. Michal Bejerano-Sagie

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  4. Hana Boocholez

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  5. Filipa Carvalhal Marques

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  6. Yuli Volovik

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  7. Tayir Elami

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  8. Atif Ahmed Siddiqui

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  9. Danielle Grushko

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  10. Adi Biram

    Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6169-9861
  11. Bar Lampert

    Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  12. Hana Achache

    Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  13. Tommer Ravid

    Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  14. Yonatan B Tzur

    Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel
    Competing interests
    The authors declare that no competing interests exist.
  15. Ehud Cohen

    Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel
    For correspondence
    ehudc@ekmd.huji.ac.il
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5552-7086

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

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: May 24, 2018
  2. Accepted: November 6, 2018
  3. Accepted Manuscript published: November 7, 2018 (version 1)

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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