title: Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans.
abstract: The transcription factor hypoxia-inducible factor 1 (HIF-1) is crucial for responses to low oxygen and promotes longevity in Caenorhabditis elegans. We previously performed a genomewide RNA interference screen and identified many genes that act as potential negative regulators of HIF-1. Here, we functionally characterized these genes and found several novel genes that affected lifespan. The worm ortholog of elongin C, elc-1, encodes a subunit of E3 ligase and transcription elongation factor. We found that knockdown of elc-1 prolonged lifespan and delayed paralysis caused by impaired protein homeostasis. We further showed that elc-1 RNA interference increased lifespan and protein homeostasis by upregulating HIF-1. The roles of elongin C and HIF-1 are well conserved in eukaryotes. Thus, our study may provide insights into the aging regulatory pathway consisting of elongin C and HIF-1 in complex metazoans.
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
authors.forename: Wooseon
authors.initials: W
authors.lastname: Hwang
authors.affiliation: Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
authors.forename: Murat
authors.initials: M
authors.lastname: Artan
authors.affiliation: School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.|Center for Plant Aging Research, Institute for Basic Science, Daegu, 42988, South Korea.
authors.forename: Mihwa
authors.initials: M
authors.lastname: Seo
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
authors.forename: Dongyeop
authors.initials: D
authors.lastname: Lee
authors.affiliation: Center for Plant Aging Research, Institute for Basic Science, Daegu, 42988, South Korea.|Department of New Biology, DGIST, Daegu, 42988, South Korea.
authors.forename: Hong Gil
authors.initials: HG
authors.lastname: Nam
authors.affiliation: Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.|Information Technology Convergence Engineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.|School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology, Pohang, Gyeongbuk, 37673, South Korea.
authors.forename: Seung-Jae V
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D000075065:Elongin; D006706:Homeostasis / Q000502:physiology; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010100:Oxygen / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D000075065:Elongin; C541178:HIF-1 protein, C elegans; D034741:RNA, Small Interfering; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; D010100:Oxygen
keywords: C. elegans; aging; elc-1; hypoxia-inducible factor 1; protein homeostasis