Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans

Heehwa G. Son; Keunhee Seo; Mihwa Seo; Sangsoon Park; Seokjin Ham; Seon Woo A. An; Eun-Seok Choi; Yujin Lee; Haeshim Baek; Eunju Kim; Youngjae Ryu; Chang Man Ha; Ao-Lin Hsu; Tae-Young Roh; Sung Key Jang; Seung-Jae V. Lee

doi:10.1101/gad.317362.118

Prefoldin 6 mediates longevity response from heat shock factor 1 to FOXO in C. elegans

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 Gyeongbuk Institute of Science and Technology, 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

Corresponding author: seungjaelee{at}postech.ac.kr

↵12 These 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

Footnotes

↵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.
Supplemental material is available for this article.
Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.317362.118.

Received May 31, 2018.
Accepted October 2, 2018.

This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.