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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.

SUBMITTER: Hwang W

PROVIDER: S-EPMC4693473 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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

Hwang Wooseon W Artan Murat M Seo Mihwa M Lee Dongyeop D Nam Hong Gil HG Lee Seung-Jae V SJ

Aging cell 20150911 6

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 ...[more]

PMID: 26361075

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