SMK-1，DAF-16介导的长寿的关键调节因子。

SMK-1, an essential regulator of DAF-16-mediated longevity.

作者信息

Wolff Suzanne, Ma Hui, Burch Denise, Maciel Gustavo A, Hunter Tony, Dillin Andrew

机构信息

Molecular and Cell Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Cell. 2006 Mar 10;124(5):1039-53. doi: 10.1016/j.cell.2005.12.042.

DOI:10.1016/j.cell.2005.12.042

PMID:16530049

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.

摘要

胰岛素/胰岛素样生长因子-1信号通路（IIS）通过一套特征明确、高度保守的核心组分来调控线虫、果蝇和小鼠的衰老过程。IIS还调控早期发育决策、动物的生殖状态、先天免疫和应激抵抗功能。在秀丽隐杆线虫中，唯一的胰岛素/胰岛素样生长因子-1受体DAF-2对FOXO转录因子DAF-16起负调控作用。我们在此报告IIS长寿途径的一个新组分SMK-1，它通过调节DAF-16活性的转录特异性，特异性地影响秀丽隐杆线虫衰老过程中DAF-16依赖性调控。对DAF-16的定位分析表明，SMK-1位于DAF-16磷酸化依赖性转位至细胞核的下游。生理和转录分析表明，smk-1是DAF-16先天免疫、紫外线和氧化应激功能所必需的，但不是热应激功能所必需的。因此，SMK-1通过调节DAF-16转录特异性在长寿中发挥作用，而不影响IIS调控的其他过程。