期刊
AUTOPHAGY
卷 17, 期 3, 页码 820-822出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2020.1861836
关键词
Autophagy; fatty acids; oleate; protein secretion; unfolded protein response
类别
资金
- Fondation pour la Recherche Medicale
- Ligue contre le Cancer (equipe labellisee)
- Agence National de la Recherche (ANR) -Projets blancs
- ANR
- AMMICa US23/CNRS UMS3655
- Association pour la recherche sur le cancer (ARC)
- Association Le Cancer du Sein, Parlonsen!
- Canceropole Ile-de-France
- Chancelerie des universites de Paris (Legs Poix), Fondation pour la Recherche Medicale (FRM)
- European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR)
- Fondation Carrefour
- Highend Foreign Expert Program in China [GDW20171100085, GDW20181100051]
- Institut National du Cancer (INCa)
- Inserm (HTE)
- Institut Universitaire de France
- LeDucq Foundation
- LabEx Immuno-Oncology [ANR-18-IDEX-0001]
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Gustave Roussy Odyssea, the European Union Horizon 2020 Project Oncobiome
Oleate blocks conventional protein secretion and induces the local enrichment of LC3 at the trans-Golgi network, independent of the recruitment of LC3 to the Golgi apparatus.
Oleate, the most abundantly occurring cis-unsaturated fatty acid, has the particularity to induce the accumulation of MAP1LC3B/LC3 (microtubule associated protein 1 light chain 3 beta) at the trans-Golgi apparatus. A genome-wide RNA interference screen designed to identify the mechanisms of this LC3 redistribution led to the identification of a BECN1-PIK3C3-independent pathway that, however, requires the ATG12-ATG5 and ATG7-dependent conjugation system, and several genes/proteins involved in endoplasmic reticulum (ER)-to-Golgi anterograde protein transport, as well as the unfolded protein response, including the integrated stress response that results in the phosphorylation of EIF2A/eIF2 alpha (eukaryotic translation initiation factor 2A). Functional experiments revealed that oleate blocks conventional protein secretion, stalling the process at the level of the trans-Golgi network. Oleate-induced blockade of protein secretion occurred even after depletion of ATG5, suggesting that it does not rely on the recruitment of LC3 to the Golgi apparatus (which does require ATG5). Rather, it appears that oleate and other pharmacological inhibitors of protein secretion with a similar mode of action provoke a perturbation of the trans-Golgi compartment that secondarily results in the local enrichment of LC3.
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