한빛사 논문
Heehwa G. Son1,12, Keunhee Seo1,12, Mihwa Seo1,2,3,4, Sangsoon Park1, Seokjin Ham1, Seon Woo A. An1, Eun-Seok Choi1,10,11, Yujin Lee1, Haeshim Baek1, Eunju Kim5, Youngjae Ryu6, Chang Man Ha6, Ao-Lin Hsu5,7,8, Tae-Young Roh1,9, Sung Key Jang1 and Seung-Jae V. Lee1,2,*
1Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
2School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea;
3Center for plant Aging Research, Institute for Basic Science, Daegu 42988, South Korea;
4Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea;
5Department of Internal Medicine, Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA;
6Research Division, Korea Brain Research Institute, Daegu 41068, South Korea;
7Research Center for Healthy Aging, China Medical University, Taichung 404, Taiwan;
8Institute of New Drug Development, China Medical University, Taichung 404, Taiwan;
9Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk 37673, South Korea
Present addresses: 10Division of Precision Medicine, Research Institute, National Cancer Center, Goyang, Gyeonggi-do 10408, South Korea;
11Department of Environmental Medical Biology, Institute of Tropical Medicine, Yonsei University College of Medicine, Seoul 03722, South Korea.
*Corresponding author: seungjaelee@postech.ac.kr
12These authors contributed equally to this work.
Abstract
Heat shock factor 1 (HSF-1) and forkhead box O (FOXO) are key transcription factors that protect cells from various stresses. In Caenorhabditis elegans, HSF-1 and FOXO together promote a long life span when insulin/IGF-1 signaling (IIS) is reduced. However, it remains poorly understood how HSF-1 and FOXO cooperate to confer IIS-mediated longevity. Here, we show that prefoldin 6 (PFD-6), a component of the molecular chaperone prefoldin-like complex, relays longevity response from HSF-1 to FOXO under reduced IIS. We found that PFD-6 was specifically required for reduced IIS-mediated longevity by acting in the intestine and hypodermis. We showed that HSF-1 increased the levels of PFD-6 proteins, which in turn directly bound FOXO and enhanced its transcriptional activity. Our work suggests that the prefoldin-like chaperone complex mediates longevity response from HSF-1 to FOXO to increase the life span in animals with reduced IIS.
Keywords: aging, C. elegans, DAF-16/FOXO, HSF-1/HSF1, PFD-6/PFDN6
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