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

Andrea C. Carrano, Andrew Dillin and Tony Hunter ()
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Andrea C. Carrano: Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies
Andrew Dillin: Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies
Tony Hunter: Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies

Nature Communications, 2014, vol. 5, issue 1, 1-9

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms4772

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