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Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans

Title
Inhibition of elongin C promotes longevity and protein homeostasis via HIF-1 in C. elegans
Authors
Hwang, W[Hwang, Wooseon]Artan, M[Artan, Murat]Seo, M[Seo, Mihwa]Lee, D[Lee, Dongyeop]Nam, HG[Nam, Hong Gil]Lee, SJV[Lee, Seung-Jae V.]
DGIST Authors
Nam, HG[Nam, Hong Gil]
Issue Date
2015-12
Citation
Aging Cell, 14(6), 995-1002
Type
Article
Article Type
Article
Keywords
AgingAmino Acid SequenceC. ElegansCaenorhabditis ElegansControlled StudyElc-1Elongin CGenetic AssociationHypoxia-Inducible Factor-1LifespanLongevityMitochondrial GeneNon-HumanPriority JournalProtein DegradationProtein HomeostasisProtein Synthesis InhibitionRegulatory MechanismRNA InterferenceTranscription Elongation FactorUpregulation
ISSN
1474-9718
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. © 2015 The Anatomical Society and John Wiley & Sons Ltd.
URI
http://hdl.handle.net/20.500.11750/1652
DOI
10.1111/acel.12390
Publisher
Wiley Blackwell
Related Researcher
Files:
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Collection:
New BiologyETC1. Journal Articles


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