Journal of Zhejiang University. B. Science, 2017, Vol.18 (1), p.1-14
2017
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Molecular signal networks and regulating mechanisms of the unfolded protein response
- Ist Teil von
- Journal of Zhejiang University. B. Science, 2017, Vol.18 (1), p.1-14
- Ort / Verlag
- Hangzhou: Zhejiang University Press
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 1α (IRE1α)). 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-γ (PLCγ)-mammalian target of rapamycin complex 1 (mTORC1) pathway, induced only in solid tumors, can also activate ATF6 and PERK signal cascades, and IRE1α 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), Ca 2+ 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1673-1581eISSN: 1862-1783DOI: 10.1631/jzus.B1600043Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5260473
- Format
- –
- Schlagworte
- Activating transcription factor 6, Activating Transcription Factor 6 - metabolism, AKT protein, Animals, Apoptosis, Biomedical and Life Sciences, Biomedicine, c-Jun protein, Calcium, Calcium ions, Cancer, Cascades, Dephosphorylation, eIF-2 Kinase - metabolism, Endoplasmic reticulum, Endoplasmic Reticulum Stress, Endoribonucleases - metabolism, Gene Expression Regulation, Heat-Shock Proteins - metabolism, Homeostasis, Humans, Immunoglobulins - chemistry, Inositol, JNK protein, Kinases, Mechanistic Target of Rapamycin Complex 1, Multiprotein Complexes - metabolism, Negative feedback, Phospholipase, Phospholipase C, Protein Domains, Protein Folding, Protein kinase, Protein-Serine-Threonine Kinases - metabolism, Proteins, Rapamycin, Reactive oxygen species, Reactive Oxygen Species - metabolism, Review, Ribonucleic acid, Ribosomes - metabolism, RNA, Sensors, Signal Transduction, Solid tumors, Stat3 protein, STAT3 Transcription Factor - metabolism, Stress, Stresses, Threonine, TOR protein, TOR Serine-Threonine Kinases - metabolism, Transcription factors, Tumors, Unfolded Protein Response, Vascular endothelial growth factor