Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The folding of secretory and membrane proteins takes place in the endoplasmic reticulum (ER). The quality of the proteins folded in the ER is carefully monitored by an ER quality control mechanism that allows only correctly folded proteins to be transported to their final destination, and misfolded or unassembled proteins to be retained in the ER and subsequently degraded in a process termed 'ER-associated degradation' (ERAD). The ERAD pathway is conserved from yeast to mammals, and plays an essential role in the maintenance of ER homeostasis, as well as in the prevention of various diseases that arise from the accumulation of aberrant proteins in the ER. In the ERAD pathway, molecular chaperones and lectin-like proteins are involved in the identification of misfolded proteins, ER-resident reductases cleave disulfide bonds in these proteins to facilitate retrograde transport to the cytosol and AAA(+) adenosine triphosphatase withdraws them from the retrotranslocation channel to the cytosol where they are degraded by the ubiquitin/proteasome system. The possible mechanisms that underlie ERAD and the various factors involved in this process are discussed in this article.
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PMID:Mechanism and components of endoplasmic reticulum-associated degradation. 1992 95

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, is the most recent example of an emergent coronavirus that poses a significant threat to human health. Virus-host interactions play a major role in the viral life cycle and disease pathogenesis, and cellular pathways such as macroautophagy/autophagy prove to be either detrimental or beneficial to viral replication and maturation. Here, we describe the literature over the past twenty years describing autophagy-coronavirus interactions. There is evidence that many coronaviruses induce autophagy, although some of these viruses halt the progression of the pathway prior to autophagic degradation. In contrast, other coronaviruses usurp components of the autophagy pathway in a non-canonical fashion. Cataloging these virus-host interactions is crucial for understanding disease pathogenesis, especially with the global challenge of SARS-CoV-2 and COVID-19. With the recognition of autophagy inhibitors, including the controversial drug chloroquine, as possible treatments for COVID-19, understanding how autophagy affects the virus will be critical going forward. Abbreviations: 3-MA: 3-methyladenine (autophagy inhibitor); AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; ATPase: adenosine triphosphatase; BMM: bone marrow macrophage; CGAS: cyclic GMP-AMP synthase; CHO: Chinese hamster ovary/cell line; CoV: coronaviruses; COVID-19: Coronavirus disease 2019; DMV: double-membrane vesicle; EAV: equine arteritis virus; EDEM1: ER degradation enhancing alpha-mannosidase like protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; GFP: green fluorescent protein; HCoV: human coronavirus; HIV: human immunodeficiency virus; HSV: herpes simplex virus; IBV: infectious bronchitis virus; IFN: interferon; LAMP1: lysosomal associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MCoV: mouse coronavirus; MERS-CoV: Middle East respiratory syndrome coronavirus; MHV: mouse hepatitis virus; NBR1: NBR1 autophagy cargo receptor; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2 (autophagy receptor that directs cargo to phagophores); nsp: non-structural protein; OS9: OS9 endoplasmic reticulum lectin; PEDV: porcine epidemic diarrhea virus; PtdIns3K: class III phosphatidylinositol 3-kinase; PLP: papain-like protease; pMEF: primary mouse embryonic fibroblasts; SARS-CoV: severe acute respiratory syndrome coronavirus; SKP2: S-phase kinase associated protein 2; SQSTM1: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; ULK1: unc-51 like autophagy activating kinase 1; Vps: vacuolar protein sorting.
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PMID:Coronavirus interactions with the cellular autophagy machinery. 3296 96


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