Tags

Type your tag names separated by a space and hit enter

SMK-1, an essential regulator of DAF-16-mediated longevity.
Cell 2006; 124(5):1039-53Cell

Abstract

Insulin/IGF-1 signaling (IIS) regulates aging in worms, flies, and mice through a well-characterized, highly conserved core set of components. IIS also regulates early developmental decisions, the reproductive status of the animal, innate immunity, and stress-resistance functions. In C. elegans, the sole insulin/IGF-1 receptor, DAF-2, negatively regulates the FOXO transcription factor, DAF-16. We report here on a new component of the IIS longevity pathway, SMK-1, which specifically influences DAF-16-dependent regulation of the aging process in C. elegans by regulating the transcriptional specificity of DAF-16 activity. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus. Physiological and transcription analyses indicate that smk-1 is required for the innate immune, UV, and oxidative stress but not the thermal stress functions of DAF-16. SMK-1 therefore plays a role in longevity by modulating DAF-16 transcriptional specificity without affecting other processes regulated by IIS.

Authors+Show Affiliations

Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.No 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

16530049

Citation

Wolff, Suzanne, et al. "SMK-1, an Essential Regulator of DAF-16-mediated Longevity." Cell, vol. 124, no. 5, 2006, pp. 1039-53.
Wolff S, Ma H, Burch D, et al. SMK-1, an essential regulator of DAF-16-mediated longevity. Cell. 2006;124(5):1039-53.
Wolff, S., Ma, H., Burch, D., Maciel, G. A., Hunter, T., & Dillin, A. (2006). SMK-1, an essential regulator of DAF-16-mediated longevity. Cell, 124(5), pp. 1039-53.
Wolff S, et al. SMK-1, an Essential Regulator of DAF-16-mediated Longevity. Cell. 2006 Mar 10;124(5):1039-53. PubMed PMID: 16530049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SMK-1, an essential regulator of DAF-16-mediated longevity. AU - Wolff,Suzanne, AU - Ma,Hui, AU - Burch,Denise, AU - Maciel,Gustavo A, AU - Hunter,Tony, AU - Dillin,Andrew, PY - 2005/05/18/received PY - 2005/10/28/revised PY - 2005/12/19/accepted PY - 2006/3/15/pubmed PY - 2006/5/5/medline PY - 2006/3/15/entrez SP - 1039 EP - 53 JF - Cell JO - Cell VL - 124 IS - 5 N2 - Insulin/IGF-1 signaling (IIS) regulates aging in worms, flies, and mice through a well-characterized, highly conserved core set of components. IIS also regulates early developmental decisions, the reproductive status of the animal, innate immunity, and stress-resistance functions. In C. elegans, the sole insulin/IGF-1 receptor, DAF-2, negatively regulates the FOXO transcription factor, DAF-16. We report here on a new component of the IIS longevity pathway, SMK-1, which specifically influences DAF-16-dependent regulation of the aging process in C. elegans by regulating the transcriptional specificity of DAF-16 activity. Localization analysis of DAF-16 places SMK-1 downstream of DAF-16's phosphorylation-dependent relocation to the nucleus. Physiological and transcription analyses indicate that smk-1 is required for the innate immune, UV, and oxidative stress but not the thermal stress functions of DAF-16. SMK-1 therefore plays a role in longevity by modulating DAF-16 transcriptional specificity without affecting other processes regulated by IIS. SN - 0092-8674 UR - https://www.unboundmedicine.com/medline/citation/16530049/SMK_1_an_essential_regulator_of_DAF_16_mediated_longevity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(06)00196-6 DB - PRIME DP - Unbound Medicine ER -