Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis
Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of t...
Ausführliche Beschreibung
Autor*in: |
Liu, Fuli [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
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2022transfer abstract |
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Umfang: |
13 |
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Übergeordnetes Werk: |
Enthalten in: Outcomes and complications of triceps tendon repair following acute rupture in American military personnel - Balazs, George C. ELSEVIER, 2016, JGG, Amsterdam [u.a.] |
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Übergeordnetes Werk: |
volume:49 ; year:2022 ; number:3 ; pages:195-207 ; extent:13 |
Links: |
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DOI / URN: |
10.1016/j.jgg.2021.08.017 |
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520 | |a Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. | ||
520 | |a Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. | ||
650 | 7 | |a ERAD |2 Elsevier | |
650 | 7 | |a Drosophila |2 Elsevier | |
650 | 7 | |a Intestinal homeostasis |2 Elsevier | |
650 | 7 | |a Derlin-1 |2 Elsevier | |
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700 | 1 | |a Zhao, Hang |4 oth | |
700 | 1 | |a Kong, Ruiyan |4 oth | |
700 | 1 | |a Shi, Lin |4 oth | |
700 | 1 | |a Li, Zhengran |4 oth | |
700 | 1 | |a Ma, Rui |4 oth | |
700 | 1 | |a Zhao, Huiqing |4 oth | |
700 | 1 | |a Li, Zhouhua |4 oth | |
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10.1016/j.jgg.2021.08.017 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001734.pica (DE-627)ELV057246211 (ELSEVIER)S1673-8527(21)00303-9 DE-627 ger DE-627 rakwb eng 610 VZ 660 VZ 660 VZ 58.10 bkl Liu, Fuli verfasserin aut Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis 2022transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. ERAD Elsevier Drosophila Elsevier Intestinal homeostasis Elsevier Derlin-1 Elsevier TER94/VCP/p97 Elsevier Zhao, Hang oth Kong, Ruiyan oth Shi, Lin oth Li, Zhengran oth Ma, Rui oth Zhao, Huiqing oth Li, Zhouhua oth Enthalten in Elsevier Balazs, George C. ELSEVIER Outcomes and complications of triceps tendon repair following acute rupture in American military personnel 2016 JGG Amsterdam [u.a.] (DE-627)ELV024886548 volume:49 year:2022 number:3 pages:195-207 extent:13 https://doi.org/10.1016/j.jgg.2021.08.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_110 GBV_ILN_121 GBV_ILN_130 GBV_ILN_370 GBV_ILN_2011 GBV_ILN_2031 GBV_ILN_2046 58.10 Verfahrenstechnik: Allgemeines VZ AR 49 2022 3 195-207 13 |
spelling |
10.1016/j.jgg.2021.08.017 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001734.pica (DE-627)ELV057246211 (ELSEVIER)S1673-8527(21)00303-9 DE-627 ger DE-627 rakwb eng 610 VZ 660 VZ 660 VZ 58.10 bkl Liu, Fuli verfasserin aut Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis 2022transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. ERAD Elsevier Drosophila Elsevier Intestinal homeostasis Elsevier Derlin-1 Elsevier TER94/VCP/p97 Elsevier Zhao, Hang oth Kong, Ruiyan oth Shi, Lin oth Li, Zhengran oth Ma, Rui oth Zhao, Huiqing oth Li, Zhouhua oth Enthalten in Elsevier Balazs, George C. ELSEVIER Outcomes and complications of triceps tendon repair following acute rupture in American military personnel 2016 JGG Amsterdam [u.a.] (DE-627)ELV024886548 volume:49 year:2022 number:3 pages:195-207 extent:13 https://doi.org/10.1016/j.jgg.2021.08.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_110 GBV_ILN_121 GBV_ILN_130 GBV_ILN_370 GBV_ILN_2011 GBV_ILN_2031 GBV_ILN_2046 58.10 Verfahrenstechnik: Allgemeines VZ AR 49 2022 3 195-207 13 |
allfields_unstemmed |
10.1016/j.jgg.2021.08.017 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001734.pica (DE-627)ELV057246211 (ELSEVIER)S1673-8527(21)00303-9 DE-627 ger DE-627 rakwb eng 610 VZ 660 VZ 660 VZ 58.10 bkl Liu, Fuli verfasserin aut Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis 2022transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. ERAD Elsevier Drosophila Elsevier Intestinal homeostasis Elsevier Derlin-1 Elsevier TER94/VCP/p97 Elsevier Zhao, Hang oth Kong, Ruiyan oth Shi, Lin oth Li, Zhengran oth Ma, Rui oth Zhao, Huiqing oth Li, Zhouhua oth Enthalten in Elsevier Balazs, George C. ELSEVIER Outcomes and complications of triceps tendon repair following acute rupture in American military personnel 2016 JGG Amsterdam [u.a.] (DE-627)ELV024886548 volume:49 year:2022 number:3 pages:195-207 extent:13 https://doi.org/10.1016/j.jgg.2021.08.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_110 GBV_ILN_121 GBV_ILN_130 GBV_ILN_370 GBV_ILN_2011 GBV_ILN_2031 GBV_ILN_2046 58.10 Verfahrenstechnik: Allgemeines VZ AR 49 2022 3 195-207 13 |
allfieldsGer |
10.1016/j.jgg.2021.08.017 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001734.pica (DE-627)ELV057246211 (ELSEVIER)S1673-8527(21)00303-9 DE-627 ger DE-627 rakwb eng 610 VZ 660 VZ 660 VZ 58.10 bkl Liu, Fuli verfasserin aut Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis 2022transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. ERAD Elsevier Drosophila Elsevier Intestinal homeostasis Elsevier Derlin-1 Elsevier TER94/VCP/p97 Elsevier Zhao, Hang oth Kong, Ruiyan oth Shi, Lin oth Li, Zhengran oth Ma, Rui oth Zhao, Huiqing oth Li, Zhouhua oth Enthalten in Elsevier Balazs, George C. ELSEVIER Outcomes and complications of triceps tendon repair following acute rupture in American military personnel 2016 JGG Amsterdam [u.a.] (DE-627)ELV024886548 volume:49 year:2022 number:3 pages:195-207 extent:13 https://doi.org/10.1016/j.jgg.2021.08.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_110 GBV_ILN_121 GBV_ILN_130 GBV_ILN_370 GBV_ILN_2011 GBV_ILN_2031 GBV_ILN_2046 58.10 Verfahrenstechnik: Allgemeines VZ AR 49 2022 3 195-207 13 |
allfieldsSound |
10.1016/j.jgg.2021.08.017 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001734.pica (DE-627)ELV057246211 (ELSEVIER)S1673-8527(21)00303-9 DE-627 ger DE-627 rakwb eng 610 VZ 660 VZ 660 VZ 58.10 bkl Liu, Fuli verfasserin aut Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis 2022transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. ERAD Elsevier Drosophila Elsevier Intestinal homeostasis Elsevier Derlin-1 Elsevier TER94/VCP/p97 Elsevier Zhao, Hang oth Kong, Ruiyan oth Shi, Lin oth Li, Zhengran oth Ma, Rui oth Zhao, Huiqing oth Li, Zhouhua oth Enthalten in Elsevier Balazs, George C. ELSEVIER Outcomes and complications of triceps tendon repair following acute rupture in American military personnel 2016 JGG Amsterdam [u.a.] (DE-627)ELV024886548 volume:49 year:2022 number:3 pages:195-207 extent:13 https://doi.org/10.1016/j.jgg.2021.08.017 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U SSG-OLC-PHA GBV_ILN_20 GBV_ILN_110 GBV_ILN_121 GBV_ILN_130 GBV_ILN_370 GBV_ILN_2011 GBV_ILN_2031 GBV_ILN_2046 58.10 Verfahrenstechnik: Allgemeines VZ AR 49 2022 3 195-207 13 |
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Enthalten in Outcomes and complications of triceps tendon repair following acute rupture in American military personnel Amsterdam [u.a.] volume:49 year:2022 number:3 pages:195-207 extent:13 |
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Enthalten in Outcomes and complications of triceps tendon repair following acute rupture in American military personnel Amsterdam [u.a.] volume:49 year:2022 number:3 pages:195-207 extent:13 |
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Outcomes and complications of triceps tendon repair following acute rupture in American military personnel |
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Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis |
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Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. |
abstractGer |
Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. |
abstract_unstemmed |
Adult stem cells are critical for the maintenance of residential tissue homeostasis and functions. However, the roles of cellular protein homeostasis maintenance in stem cell proliferation and tissue homeostasis are not fully understood. Here, we find that Derlin-1 and TER94/VCP/p97, components of the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, restrain intestinal stem cell proliferation to maintain intestinal homeostasis in adult Drosophila. Depleting any of them results in increased stem cell proliferation and midgut homeostasis disruption. Derlin-1 is specifically localized in the ER of progenitors, and its C-terminus is required for its function. Interestingly, we find that increased stem cell proliferation is resulted from elevated ROS levels and activated JNK signaling in Derlin-1- or TER94-deficient progenitors. Further removal of reactive oxygen species (ROS) or inhibition of JNK signaling almost completely suppresses increased stem cell proliferation. Together, these data demonstrate that the ERAD pathway is critical for stem cell proliferation and tissue homeostasis. Thus, we provide insights into our understanding of the mechanisms underlying cellular protein homeostasis maintenance (ER protein quality control) in tissue homeostasis and tumor development. |
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Derlin-1 and TER94/VCP/p97 are required for intestinal homeostasis |
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