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A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans

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  • Andrea C. Carrano

    (Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies
    Present address: Department of Pediatrics, University of California, San Diego, La Jolla, California 92093, USA)

  • Andrew Dillin

    (Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies
    The Howard Hughes Medical Institute, University of California)

  • Tony Hunter

    (Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies)

Abstract

The HECT ubiquitin E3 ligase WWP-1 is a positive regulator of lifespan in response to dietary restriction (DR) in Caenorhabditis elegans. However, substrates of WWP-1 for ubiquitylation in the DR pathway have not yet been identified. Here we identify the C. elegans Krüppel-like factor, KLF-1, as an essential and specific regulator of DR-induced longevity and a substrate for ubiquitylation by WWP-1. Knockdown of klf-1 suppresses the extended lifespan of both DR animals and wwp-1-overexpressing animals, indicating that KLF-1 functions within the same pathway as WWP-1. In addition, overexpression of klf-1 in the intestine is sufficient to extend the lifespan of WT animals on an ad libitum diet, and requires wwp-1 or pha-4/FoxA. We demonstrate that WWP-1 directly interacts with KLF-1 and mediates multiple monoubiquitylation of KLF-1 in vitro and in cellulo. Our data support a model in which modulation of KLF-1 by WWP-1 regulates diet-restriction-induced longevity.

Suggested Citation

  • Andrea C. Carrano & Andrew Dillin & Tony Hunter, 2014. "A Krüppel-like factor downstream of the E3 ligase WWP-1 mediates dietary-restriction-induced longevity in Caenorhabditis elegans," Nature Communications, Nature, vol. 5(1), pages 1-9, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4772
    DOI: 10.1038/ncomms4772
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