Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body...Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.展开更多
Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the ...Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.展开更多
文摘Efficient functioning of the endoplasmic reticulum(ER) is very important for most cellular activities, such as protein folding and modification. The ER closely interacts with other organelles, including the Golgi body, endosome, membrane, and mitochondria, providing lipids and proteins for the repair of these organelles. ER stress can be induced by various abnormal materials in the cell. ER stress is a compensatory intracellular environment disorder that occurs during areaction. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system, but excessive ER activation can cause cell death. The Pubmed and Web of Science databases were searched for full-text articles, and the terms "endoplasmic reticulum stress/unfolded protein response/gynecologic tumor cell apoptosis" were used as key words. Thirty-five studies of ER stress and unfolded protein response published from 2000 to 2016 were analyzed. Stress triggers apoptosis through a variety of signaling pathways. Increasing evidence has shown that the ER plays an important role in tumor cell diseases. The present review discusses the molecular mechanisms underlying unfolded protein response and its ability to promote survival and proliferation in gynecologic tumor cells.
基金Project supported by the National Basic Research Program(973)of China(No.2012CB518900)the National Natural Science Foundation of China(Nos.31160240 and 31260621)+2 种基金the National Major Scientific and Technological Special Project during the Twelfth Five-year Plan Period of China(No.2012ZX10002006)the Hangzhou Normal University Supporting Project(No.PE13002004042)the Natural Science Foundation of Jiangxi Province(No.20114BAB204016),China
文摘Within the cell, several mechanisms exist to maintain homeostasis of the endoplasmic reticulum （ER）. One of the primary mechanisms is the unfolded protein response （UPR）. In this review, we primarily focus on the latest signal webs and regulation mechanisms of the UPR. The relationships among ER stress, apoptosis, and cancer are also discussed. Under the normal state, binding immunoglobulin protein （BiP） interacts with the three sensors （protein kinase RNA-like ER kinase （PERK）, activating transcription factor 6 （ATF6）, and inositol-requiring enzyme la （IREla）） Under ER stress, misfolded proteins interact with BiP, resulting in the release of BiP from the sensors. Subsequently, the three sensors dimerize and autophosphorylate to promote the signal cascades of ER stress. ER stress includes a series of positive and negative feedback signals, such as those regulating the stabilization of the sensors/BiP complex, activating and inactivating the sensors by autophosphorylation and dephosphorylation, activating specific transcription factors to enable selective transcription, and augmenting the ability to refold and export. Apart from the three basic pathways, vascular endothelial growth factor （VEGF）-VEGF receptor （VEGFR）-phospholipase C-~ （PLCy）-mammalian target of rapamycin complex 1 （mTORC1） pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IREla also can be activated by activated RAC-alpha serine/threonine-protein kinase （AKT）. A moderate UPR functions as a pro-survival signal to return the cell to its state of homeostasis. However, persistent ER stress will induce cells to undergo apoptosis in response to increasing reactive oxygen species （ROS）, Ca2＋ in the cytoplasmic matrix, and other apoptosis signal cascades, such as c-Jun N-terminal kinase （JNK）, signal transducer and activator of transcription 3 （STAT3）, and P38, when cellular damage exceeds the capacity of this adaptive response.
