期刊
SCIENCE ADVANCES
卷 5, 期 7, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aaw2238
关键词
-
资金
- American Cancer Society [RSG-16-014-01-CDD]
- U.S. National Institutes of Health [R01CA211070, GM131919, R01CA181450, R01CA206012]
- National Natural Science Foundation of China [81830048, 81772508, 31671435, 81570154, 81100359]
- Natural Science Foundation of Hunan Province [2016JJ3171]
- Ligue contre le Cancer Comite de Charente-Maritime (equipe labellisee)
- Agence National de la Recherche (ANR)-Programme Blanc
- ANR under E-Rare-2 (the ERA-Net for Research on Rare Diseases)
- Association pour la recherche sur le cancer (ARC)
- Canceropole Ile-de-France
- Chancellerie des universites de Paris (Legs Poix)
- Fondation pour la Recherche Medicale (FRM)
- European Commission (ArtForce)
- European Research Council (ERC)
- Fondation Carrefour
- Institut National du Cancer (INCa)
- INSERM [Heterogeneity of Tumors & Ecosystem (HTE) Program]
- Institut Universitaire de France
- Leducq Foundation
- LabEx Immuno-Oncology
- RHU Torino Lumiere
- Seerave Foundation
- SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE)
- SIRIC Cancer Research and Personalized Medicine (CARPEM)
- Paris Alliance of Cancer Research Institutes (PACRI)
Ferroptosis is a form of nonapoptotic regulated cell death driven by iron-dependent lipid peroxidation. Autophagy involves a lysosomal degradation pathway that can either promote or impede cell death. A high level of autophagy has been associated with ferroptosis, but the mechanisms underpinning this relationship are largely elusive. We characterize the contribution of autophagy to ferroptosis in human cancer cell lines and mouse tumor models. We show that clockophagy, the selective degradation of the core circadian clock protein ARNTL by autophagy, is critical for ferroptosis. We identify SQSTM1 as a cargo receptor responsible for autophagic ARNTL degradation. ARNTL inhibits ferroptosis by repressing the transcription of Egln2, thus activating the prosurvival transcription factor HIF1 A. Genetic or pharmacological interventions blocking ARNTL degradation or inhibiting EGLN2 activation diminished, whereas destabilizing HIFI A facilitated, ferroptotic tumor cell death. Thus, our findings reveal a new pathway, initiated by the autophagic removal of ARNTL, that facilitates ferroptosis induction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据