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Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans.
Cell. 2008 Mar 21; 132(6):1025-38.Cell

Abstract

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 IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that 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.

Authors+Show Affiliations

Section on Developmental and Stem Cell Biology, Joslin Diabetes Center; Department of Pathology, Harvard Medical School; Harvard Stem Cell Institute, 1 Joslin Place, Boston, MA 02215, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18358814

Citation

Tullet, Jennifer M A., et al. "Direct Inhibition of the Longevity-promoting Factor SKN-1 By Insulin-like Signaling in C. Elegans." Cell, vol. 132, no. 6, 2008, pp. 1025-38.
Tullet JM, Hertweck M, An JH, et al. Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell. 2008;132(6):1025-38.
Tullet, J. M., Hertweck, M., An, J. H., Baker, J., Hwang, J. Y., Liu, S., Oliveira, R. P., Baumeister, R., & Blackwell, T. K. (2008). Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. Cell, 132(6), 1025-38. https://doi.org/10.1016/j.cell.2008.01.030
Tullet JM, et al. Direct Inhibition of the Longevity-promoting Factor SKN-1 By Insulin-like Signaling in C. Elegans. Cell. 2008 Mar 21;132(6):1025-38. PubMed PMID: 18358814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans. AU - Tullet,Jennifer M A, AU - Hertweck,Maren, AU - An,Jae Hyung, AU - Baker,Joseph, AU - Hwang,Ji Yun, AU - Liu,Shu, AU - Oliveira,Riva P, AU - Baumeister,Ralf, AU - Blackwell,T Keith, PY - 2007/06/29/received PY - 2007/12/18/revised PY - 2008/01/18/accepted PY - 2008/3/25/pubmed PY - 2008/4/12/medline PY - 2008/3/25/entrez SP - 1025 EP - 38 JF - Cell JO - Cell VL - 132 IS - 6 N2 - 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 IIS-inhibited FOXO protein DAF-16. The C. elegans transcription factor SKN-1 also defends against oxidative stress by mobilizing the conserved phase 2 detoxification response. Here we show that 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. SN - 1097-4172 UR - https://www.unboundmedicine.com/medline/citation/18358814/Direct_inhibition_of_the_longevity_promoting_factor_SKN_1_by_insulin_like_signaling_in_C__elegans_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(08)00130-X DB - PRIME DP - Unbound Medicine ER -