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

Authors: Carrano, Andrea C; Dillin, Andrew; Hunter, Tony

Published In Nat Commun, (2014 May 08)

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.

PubMed ID: 24805825

MeSH Terms: Animals; Animals, Genetically Modified; Caenorhabditis elegans Proteins/biosynthesis; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism*; Caenorhabditis elegans/physiology*; Caloric Restriction*; Diet/methods; Intestines/metabolism; Kruppel-Like Transcription Factors/biosynthesis; Kruppel-Like Transcription Factors/genetics; Kruppel-Like Transcription Factors/metabolism*; Longevity/genetics; RNA Interference; RNA, Small Interfering; Trans-Activators/metabolism; Ubiquitin-Protein Ligases/biosynthesis; Ubiquitin-Protein Ligases/genetics; Ubiquitin-Protein Ligases/metabolism*; Ubiquitination