Open AccessInhibition of elongin C promotes longevity and protein homeostasis via HIF ‐1 in C. elegans
Author(s) -
Hwang Wooseon,
Artan Murat,
Seo Mihwa,
Lee Dongyeop,
Nam Hong Gil,
Lee SeungJae V.
Publication year - 2015
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12390
Subject(s) - biology , caenorhabditis elegans , rna interference , transcription factor , gene knockdown , longevity , microbiology and biotechnology , protein subunit , gene , genetics , transcription (linguistics) , rna , linguistics , philosophy
Summary 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.