Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusinopen access
- Authors
- Park, Ye-Jin; Choi, Dong Wook; Cho, Sang Woo; Han, Jaeseok; Yang, Siyoung; Choi, Cheol Yong
- Issue Date
- Aug-2020
- Publisher
- Multidisciplinary Digital Publishing Institute (MDPI)
- Keywords
- stress granule; morusin; PKR; eIF2 alpha; RACK1; cell death
- Citation
- International Journal of Molecular Sciences, v.21, no.15
- Journal Title
- International Journal of Molecular Sciences
- Volume
- 21
- Number
- 15
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/2609
- DOI
- 10.3390/ijms21155360
- ISSN
- 1661-6596
1422-0067
- Abstract
- Stress granules are membraneless organelles composed of numerous components including ribonucleoproteins. The stress granules are characterized by a dynamic complex assembly in response to various environmental stressors, which has been implicated in the coordinated regulation of diverse biological pathways, to exert a protective role against stress-induced cell death. Here, we show that stress granule formation is induced by morusin, a novel phytochemical displaying antitumor capacity through barely known mechanisms. Morusin-mediated induction of stress granules requires activation of protein kinase R (PKR) and subsequent eIF2 alpha phosphorylation. Notably, genetic inactivation of stress granule formation mediated by G3BP1 knockout sensitized cancer cells to morusin treatment. This protective function against morusin-mediated cell death can be attributed at least in part to the sequestration of receptors for activated C kinase-1 (RACK1) within the stress granules, which reduces caspase-3 activation. Collectively, our study provides biochemical evidence for the role of stress granules in suppressing the antitumor capacity of morusin, proposing that morusin treatment, together with pharmacological inhibition of stress granules, could be an efficient strategy for targeting cancer.
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- Appears in
Collections - Graduate School > Department of Integrated Biomedical Science > 1. Journal Articles
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