Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin

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...
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Autor*in:	Ye-Jin Park [verfasserIn] Dong Wook Choi [verfasserIn] Sang Woo Cho [verfasserIn] Jaeseok Han [verfasserIn] Siyoung Yang [verfasserIn] Cheol Yong Choi [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	stress granule morusin PKR eIF2α RACK1 cell death

Übergeordnetes Werk:	In: International Journal of Molecular Sciences - MDPI AG, 2003, 21(2020), 15, p 5360
Übergeordnetes Werk:	volume:21 ; year:2020 ; number:15, p 5360

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.3390/ijms21155360

Katalog-ID:	DOAJ032374593

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520			\|a 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 eIF2α 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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allfields	10.3390/ijms21155360 doi (DE-627)DOAJ032374593 (DE-599)DOAJ20742b156a3c4de095257d9326794a15 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Ye-Jin Park verfasserin aut Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 eIF2α 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. stress granule morusin PKR eIF2α RACK1 cell death Biology (General) Chemistry Dong Wook Choi verfasserin aut Sang Woo Cho verfasserin aut Jaeseok Han verfasserin aut Siyoung Yang verfasserin aut Cheol Yong Choi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 15, p 5360 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:15, p 5360 https://doi.org/10.3390/ijms21155360 kostenfrei https://doaj.org/article/20742b156a3c4de095257d9326794a15 kostenfrei https://www.mdpi.com/1422-0067/21/15/5360 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 15, p 5360
spelling	10.3390/ijms21155360 doi (DE-627)DOAJ032374593 (DE-599)DOAJ20742b156a3c4de095257d9326794a15 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Ye-Jin Park verfasserin aut Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 eIF2α 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. stress granule morusin PKR eIF2α RACK1 cell death Biology (General) Chemistry Dong Wook Choi verfasserin aut Sang Woo Cho verfasserin aut Jaeseok Han verfasserin aut Siyoung Yang verfasserin aut Cheol Yong Choi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 15, p 5360 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:15, p 5360 https://doi.org/10.3390/ijms21155360 kostenfrei https://doaj.org/article/20742b156a3c4de095257d9326794a15 kostenfrei https://www.mdpi.com/1422-0067/21/15/5360 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 15, p 5360
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allfieldsGer	10.3390/ijms21155360 doi (DE-627)DOAJ032374593 (DE-599)DOAJ20742b156a3c4de095257d9326794a15 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Ye-Jin Park verfasserin aut Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 eIF2α 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. stress granule morusin PKR eIF2α RACK1 cell death Biology (General) Chemistry Dong Wook Choi verfasserin aut Sang Woo Cho verfasserin aut Jaeseok Han verfasserin aut Siyoung Yang verfasserin aut Cheol Yong Choi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 15, p 5360 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:15, p 5360 https://doi.org/10.3390/ijms21155360 kostenfrei https://doaj.org/article/20742b156a3c4de095257d9326794a15 kostenfrei https://www.mdpi.com/1422-0067/21/15/5360 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 15, p 5360
allfieldsSound	10.3390/ijms21155360 doi (DE-627)DOAJ032374593 (DE-599)DOAJ20742b156a3c4de095257d9326794a15 DE-627 ger DE-627 rakwb eng QH301-705.5 QD1-999 Ye-Jin Park verfasserin aut Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin 2020 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 eIF2α 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. stress granule morusin PKR eIF2α RACK1 cell death Biology (General) Chemistry Dong Wook Choi verfasserin aut Sang Woo Cho verfasserin aut Jaeseok Han verfasserin aut Siyoung Yang verfasserin aut Cheol Yong Choi verfasserin aut In International Journal of Molecular Sciences MDPI AG, 2003 21(2020), 15, p 5360 (DE-627)316340715 (DE-600)2019364-6 14220067 nnns volume:21 year:2020 number:15, p 5360 https://doi.org/10.3390/ijms21155360 kostenfrei https://doaj.org/article/20742b156a3c4de095257d9326794a15 kostenfrei https://www.mdpi.com/1422-0067/21/15/5360 kostenfrei https://doaj.org/toc/1661-6596 Journal toc kostenfrei https://doaj.org/toc/1422-0067 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 21 2020 15, p 5360
language	English
source	In International Journal of Molecular Sciences 21(2020), 15, p 5360 volume:21 year:2020 number:15, p 5360
sourceStr	In International Journal of Molecular Sciences 21(2020), 15, p 5360 volume:21 year:2020 number:15, p 5360
format_phy_str_mv	Article
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topic_facet	stress granule morusin PKR eIF2α RACK1 cell death Biology (General) Chemistry
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container_title	International Journal of Molecular Sciences
authorswithroles_txt_mv	Ye-Jin Park @@aut@@ Dong Wook Choi @@aut@@ Sang Woo Cho @@aut@@ Jaeseok Han @@aut@@ Siyoung Yang @@aut@@ Cheol Yong Choi @@aut@@
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callnumber-first	Q - Science
author	Ye-Jin Park
spellingShingle	Ye-Jin Park misc QH301-705.5 misc QD1-999 misc stress granule misc morusin misc PKR misc eIF2α misc RACK1 misc cell death misc Biology (General) misc Chemistry Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin
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topic_title	QH301-705.5 QD1-999 Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin stress granule morusin PKR eIF2α RACK1 cell death
topic	misc QH301-705.5 misc QD1-999 misc stress granule misc morusin misc PKR misc eIF2α misc RACK1 misc cell death misc Biology (General) misc Chemistry
topic_unstemmed	misc QH301-705.5 misc QD1-999 misc stress granule misc morusin misc PKR misc eIF2α misc RACK1 misc cell death misc Biology (General) misc Chemistry
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title	Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin
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title_full	Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin
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title_sort	stress granule formation attenuates rack1-mediated apoptotic cell death induced by morusin
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title_auth	Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin
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 eIF2α 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.
abstractGer	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 eIF2α 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.
abstract_unstemmed	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 eIF2α 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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title_short	Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin
url	https://doi.org/10.3390/ijms21155360 https://doaj.org/article/20742b156a3c4de095257d9326794a15 https://www.mdpi.com/1422-0067/21/15/5360 https://doaj.org/toc/1661-6596 https://doaj.org/toc/1422-0067
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up_date	2024-07-04T00:58:58.466Z
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Stress Granule Formation Attenuates RACK1-Mediated Apoptotic Cell Death Induced by Morusin

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