Inhibition of elongin C promotes longevity and protein homeostasis via…

DOI: http://dx.doi.org/10.1111/acel.12390

Wooseon Hwang, Murat Artan, Mihwa Seo, Dongyeop Lee, Hong Gil Nam, and Seung-Jae V. Lee.

Published: 11 SEP 2015.

Abstract
The transcription factor hypoxia-inducible factor 1 (HIF-1) iscrucial for responses to low oxygen and promotes longevity inCaenorhabditis elegans. We previously performed a genome-wide RNA interference screen and identified many genes that actas potential negative regulators of HIF-1. Here, we functionallycharacterized these genes and found several novel genes thataffected lifespan. The worm ortholog of elongin C, elc-1, encodesa subunit of E3 ligase and transcription elongation factor. Wefound that knockdown of elc-1 prolonged lifespan and delayedparalysis caused by impaired protein homeostasis. We furthershowed that elc-1 RNA interference increased lifespan andprotein homeostasis by upregulating HIF-1. The roles of elonginC and HIF-1 are well conserved in eukaryotes. Thus, our studymay provide insights into the aging regulatory pathway consist-ing of elongin C and HIF-1 in complex metazoans.Key words: aging; C. elegans; elc-1; hypoxia-inducible factor1; protein homeostasis.

Keywords: aging; C. elegans; elc-1; hypoxia-inducible factor 1; protein homeostasis

Link: http://onlinelibrary.wiley.com/doi/10.1111/acel.12390/full