A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans.

Ingrid Masse (1, 2) , Laurent Molin (3, 1) , Laurent Mouchiroud (1) , Philippe Vanhems (4, 5) , Francesca Palladino (6) , Marc Billaud (1) , Florence Solari (2)

1 GMSC - Génétique moléculaire, signalisation et cancer
2 CGPhiMC - Centre de génétique et de physiologie moléculaire et cellulaire
3 UCBL - Université Claude Bernard Lyon 1
4 Service d'Hygiène, Epidémiologie et Prévention [Hôpital Edouard Herriot - HCL]
5 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
6 LBMC - Laboratoire de Biologie Moléculaire de la Cellule

The PTEN tumour suppressor encodes a phosphatase, and its daf-18 orthologue in Caenorhabditis elegans negatively regulates the insulin/IGF-1 DAF-2 receptor pathway that influences lifespan in worms and other species. In order to identify new DAF-18 regulated pathways involved in aging, we initiated a candidate RNAi feeding screen for clones that lengthen lifespan. Here, we report that smg-1 inactivation increases average lifespan in a daf-18 dependent manner. Genetic analysis is consistent with SMG-1 acting at least in part in parallel to the canonical DAF-2 receptor pathway, but converging on the transcription factor DAF-16/FOXO. SMG-1 is a serine-threonine kinase which plays a conserved role in nonsense-mediated mRNA decay (NMD) in worms and mammals. In addition, human SMG-1 has also been implicated in the p53-mediated response to genotoxic stress. The effect of smg-1 inactivation on lifespan appears to be unrelated to its NMD function, but requires the p53 tumour suppressor orthologue cep-1. Furthermore, smg-1 inactivation confers a resistance to oxidative stress in a daf-18-, daf-16- and cep-1-dependent manner. We propose that the role of SMG-1 in lifespan regulation is at least partly dependent on its function in oxidative stress resistance. Taken together, our results unveil a novel role for SMG-1 in lifespan regulation.

Mots clés: Oxidative Stress; Protein Kinases; RNA Interference; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Genes; Helminth; Longevity

Domaines: Biologie moléculaire

Ingrid Masse, Laurent Molin, Laurent Mouchiroud, Philippe Vanhems, Francesca Palladino, et al.. A novel role for the SMG-1 kinase in lifespan and oxidative stress resistance in Caenorhabditis elegans.. PLoS ONE, 2008, 3 (10), pp.e3354. ⟨10.1371/journal.pone.0003354⟩. ⟨hal-00720065⟩