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Mol Oncol. 2015 Apr;9(4):806-17. doi: 10.1016/j.molonc.2014.12.004. Epub 2014 Dec 30.

RIP1 modulates death receptor mediated apoptosis and autophagy in macrophages.

Author information

1
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China; Institute of Biomedical and Health Engineering Shenzhen Institutes of Advanced Technology, CAS, China.
2
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China.
3
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China. Electronic address: zhengdx2008@gmail.com.

Abstract

Macrophages are responsible for defending against diverse pathogens and play a crucial role in the innate immune system. Macrophage's lifespan is determined by homeostatic balance between survival and apoptosis. Here we report that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers both apoptosis and autophagy in human U937 cells. Inhibition of autophagy facilitates TRAIL-induced apoptosis, suggesting that autophagy of macrophages protects against TRAIL-induced apoptosis. TRAIL treatment influences the expression of death receptors, indicating that TRAIL-induced apoptosis and autophagy are mediated by death receptors. RIP1 ubiquitination and expression regulate apoptosis and autophagy. Furthermore, expression and bioactivity of the p43/41-caspase-8 variant are critical to TRAIL-induced autophagy and apoptosis. Knockdown of RIP1 suppresses autophagy in macrophage. These data demonstrate that RIP1 is essential for the regulation of death receptor mediated autophagy and apoptosis. The results in this study contribute to understanding the regulation of autophagy and apoptosis in macrophages, and shed lights on death receptor-targeted therapy for cancer, inflammation and autoimmune diseases.

KEYWORDS:

Apoptosis; Autophagy; Death; RIP1; Tumor necrosis factor-related apoptosis-inducing ligand; Ubiquitination

PMID:
25583602
PMCID:
PMC5528779
DOI:
10.1016/j.molonc.2014.12.004
[Indexed for MEDLINE]
Free PMC Article

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