Tullet, Jennifer M. A.Hertweck, MarenAn, Jae HyungBaker, JosephHwang, Ji YunLiu, ShuOliveira, Riva de PaulaBaumeister, RalfBlackwell, T. Keith2015-03-312015-03-312008TULLET, J. M. A. et al. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell, v. 132, p. 1025-1038, 2008. Disponível em: <http://www.sciencedirect.com/science/article/pii/S009286740800130X>. Acesso em: 15 out. 2014.0092-8674http://www.repositorio.ufop.br/handle/123456789/4847Insulin/IGF-1-like signaling (IIS) is central to growth and metabolism and has a conserved role in aging. In C. elegans, reductions in IIS increase stress resistance and longevity, effects that require the IISinhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress bymobilizing the conserved phase 2 detoxification response. Herewe showthat IIS not only opposes DAF-16 but also directly inhibits SKN-1 in parallel. The IIS kinases AKT-1, -2, and SGK-1 phosphorylate SKN-1, and reduced IIS leads to constitutive SKN-1 nuclear accumulation in the intestine and SKN-1 target gene activation. SKN-1 contributes to the increased stress tolerance and longevity resulting from reduced IIS and delays aging when expressed transgenically. Furthermore, SKN-1 that is constitutively active increases life span independently of DAF-16. Our findings indicate that the transcription network regulated by SKN-1 promotes longevity and is an important direct target of IIS.en-USArtigo publicado em periodicoO periódico Cell concede permissão para depósito deste artigo no Repositório Institucional da UFOP. Número da licença: 3493711392245.https://doi.org/10.1016/j.cell.2008.01.030