Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans.

• Autor(a) principal: Tullet, Jennifer M. A.
• Data de Publicação: 2008
• Outros Autores: Hertweck, Maren, An, Jae Hyung, Baker, Joseph, Hwang, Ji Yun, Liu, Shu, Oliveira, Riva de Paula, Baumeister, Ralf, Blackwell, T. Keith
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFOP
• Texto Completo: http://www.repositorio.ufop.br/handle/123456789/4847; https://doi.org/10.1016/j.cell.2008.01.030

Insulin/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.