RRC ID 45844
著者 Safra M, Fickentscher R, Levi-Ferber M, Danino YM, Haviv-Chesner A, Hansen M, Juven-Gershon T, Weiss M, Henis-Korenblit S.
タイトル The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum homeostasis.
ジャーナル Cell Metab
Abstract The unfolded protein response (UPR) allows cells to adjust the capacity of the endoplasmic reticulum (ER) to the load of ER-associated tasks. We show that activation of the Caenorhabditis elegans transcription factor DAF-16 and its human homolog FOXO3 restore secretory protein metabolism when the UPR is dysfunctional.We show that DAF-16 establishes alternative ER-associated degradation systems that degrade misfolded proteins independently of the ER stress sensor ire-1 and the ER-associated E3 ubiquitin ligase complex sel-11/sel-1. This is achieved by enabling autophagy-mediated degradation and by increasing the levels of skr-5, a component of an ER associated ubiquitin ligase complex. These degradation systems can act together with the conserved UPR to improve ER homeostasis and ER stress resistance, beyond wild-type levels. Because there is no sensor in the ER that activates DAF-16 in response to intrinsic ER stress, natural or artificial interventions that activate DAF-16 may be useful therapeutic approaches to maintain ER homeostasis.
巻・号 20(5)
ページ 870-881
公開日 2014-11-4
DOI 10.1016/j.cmet.2014.09.006
PII S1550-4131(14)00403-3
PMID 25448701
MeSH Animals Autophagy Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Endoplasmic Reticulum Stress Endoplasmic Reticulum-Associated Degradation* Forkhead Box Protein O3 Forkhead Transcription Factors / metabolism* HEK293 Cells Humans Mutation Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism* Unfolded Protein Response
IF 21.567
引用数 13
WOS 分野 ENDOCRINOLOGY & METABOLISM CELL BIOLOGY
リソース情報
線虫 tm2457