GRP78 at the centre of the stage in cancer and neuroprotection
| Autor: | Caty Casas |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
GRP78 autophagy BiP Review Endoplasmic-reticulum-associated protein degradation Biology Neuroprotection 03 medical and health sciences medicine Autophagy Neurodegeneration Protein kinase B PI3K/AKT/mTOR pathway General Neuroscience Endoplasmic reticulum neurodegeneration ERAD medicine.disease Cytoprotection 030104 developmental biology Unfolded protein response neuroprotection endogenous mechanisms ER stress Endogenous mechanisms Neuroscience |
| Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Frontiers in Neuroscience Recercat. Dipósit de la Recerca de Catalunya instname Recercat: Dipósit de la Recerca de Catalunya Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Popis: | The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes. Hence, GRP78 may control either UPR and macroautophagy or may activated phosphatidylinositol 3-kinase (PI3K)/AKT pro-survival pathways. GRP78 influences how tumor cells survive, proliferate, and develop chemoresistance. In neurodegeneration, endogenous mechanisms of neuroprotection are frequently insufficient or dysregulated. Lessons from tumor biology may give us clues about how boosting endogenous neuroprotective mechanisms in age-related neurodegeneration. Herein, the functions of GRP78 are revealed at the center of the stage of apparently opposite sites of the same coin regarding cytoprotection: neurodegeneration and cancer. The goal is to give a comprehensive and critical review that may serve to guide future experiments to identify interventions that will enhance neuroprotection. The 78-kDa glucose-regulated protein GRP78, also known as BiP and HSP5a, is a multifunctional protein with activities far beyond its well-known role in the unfolded protein response (UPR) which is activated after endoplasmic reticulum (ER) stress in the cells. Most of these newly discovered activities depend on its position within the cell. GRP78 is located mainly in the ER, but it has also been observed in the cytoplasm, the mitochondria, the nucleus, the plasma membrane, and secreted, although it is dedicated mostly to engage endogenous cytoprotective processes. Hence, GRP78 may control either UPR and macroautophagy or may activated phosphatidylinositol 3-kinase (PI3K)/AKT pro-survival pathways. GRP78 influences how tumor cells survive, proliferate, and develop chemoresistance. In neurodegeneration, endogenous mechanisms of neuroprotection are frequently insufficient or dysregulated. Lessons from tumor biology may give us clues about how boosting endogenous neuroprotective mechanisms in age-related neurodegeneration. Herein, the functions of GRP78 are revealed at the center of the stage of apparently opposite sites of the same coin regarding cytoprotection: neurodegeneration and cancer. The goal is to give a comprehensive and critical review that may serve to guide future experiments to identify interventions that will enhance neuroprotection. |
| Databáze: | OpenAIRE |
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