RRC ID 46154
Author Liu G, Rogers J, Murphy CT, Rongo C.
Title EGF signalling activates the ubiquitin proteasome system to modulate C. elegans lifespan.
Journal EMBO J
Abstract Epidermal growth factor (EGF) signalling regulates growth and differentiation. Here, we examine the function of EGF signalling in Caenorhabditis elegans lifespan. We find that EGF signalling regulates lifespan via the Ras-MAPK pathway and the PLZF transcription factors EOR-1 and EOR-2. As animals enter adulthood, EGF signalling upregulates the expression of genes involved in the ubiquitin proteasome system (UPS), including the Skp1-like protein SKR-5, while downregulating the expression of HSP16-type chaperones. Using reporters for global UPS activity, protein aggregation, and oxidative stress, we find that EGF signalling alters protein homoeostasis in adults by increasing UPS activity and polyubiquitination, while decreasing protein aggregation. We show that SKR-5 and the E3/E4 ligases that comprise the ubiquitin fusion degradation (UFD) complex are required for the increase in UPS activity observed in adults, and that animals that lack SKR-5 or the UFD have reduced lifespans and indications of oxidative stress. We propose that as animals enter fertile adulthood, EGF signalling switches the mechanism for maintaining protein homoeostasis from a chaperone-based approach to an approach involving protein elimination via augmented UPS activity.
Volume 30(15)
Pages 2990-3003
Published 2011-6-14
DOI 10.1038/emboj.2011.195
PII emboj2011195
PMID 21673654
PMC PMC3160178
MeSH Aging / physiology Animals Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism* Epidermal Growth Factor / metabolism* Kruppel-Like Transcription Factors / metabolism Molecular Chaperones / metabolism Nuclear Proteins / metabolism Proteasome Endopeptidase Complex / metabolism* Signal Transduction* Ubiquitin / metabolism*
IF 9.889
Times Cited 63
C.elegans tm1380 tm544 tm659