38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      GRP78: A cell's response to stress

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Glucose-Regulated Protein 78 (GRP78) is a chaperone heat shock protein that has been intensely studied in the last two decades. GRP78 is the master of the unfolded protein response (UBR) in the Endoplasmic Reticulum (ER) in normal cells. GRP78 force the unfolded proteins to refold or degrade using cellular degradation mechanisms.

          Scope

          Under stress, the overexpression of GRP78 on the cell membrane mediates the vast amount of disordered proteins. Unfortunately, this makes it a tool for pathogens (bacterial, fungal and viral) to enter the cell and to start different pathways leading to pathogenesis. Additionally, GRP78 is overexpressed on the membranes of various cancer cells and increase the aggressiveness of the disease.

          Major conclusions

          The current review summarizes structure, function, and different mechanisms GRP78 mediate in response to normal or stress conditions.

          General significance

          GRP78 targeting and possible inhibition mechanisms are also covered in the present review aiming to prevent the virulence of pathogens and cancer.

          Graphical abstract

          Related collections

          Most cited references87

          • Record: found
          • Abstract: found
          • Article: not found

          Middle East respiratory syndrome coronavirus: another zoonotic betacoronavirus causing SARS-like disease.

          The source of the severe acute respiratory syndrome (SARS) epidemic was traced to wildlife market civets and ultimately to bats. Subsequent hunting for novel coronaviruses (CoVs) led to the discovery of two additional human and over 40 animal CoVs, including the prototype lineage C betacoronaviruses, Tylonycteris bat CoV HKU4 and Pipistrellus bat CoV HKU5; these are phylogenetically closely related to the Middle East respiratory syndrome (MERS) CoV, which has affected more than 1,000 patients with over 35% fatality since its emergence in 2012. All primary cases of MERS are epidemiologically linked to the Middle East. Some of these patients had contacted camels which shed virus and/or had positive serology. Most secondary cases are related to health care-associated clusters. The disease is especially severe in elderly men with comorbidities. Clinical severity may be related to MERS-CoV's ability to infect a broad range of cells with DPP4 expression, evade the host innate immune response, and induce cytokine dysregulation. Reverse transcription-PCR on respiratory and/or extrapulmonary specimens rapidly establishes diagnosis. Supportive treatment with extracorporeal membrane oxygenation and dialysis is often required in patients with organ failure. Antivirals with potent in vitro activities include neutralizing monoclonal antibodies, antiviral peptides, interferons, mycophenolic acid, and lopinavir. They should be evaluated in suitable animal models before clinical trials. Developing an effective camel MERS-CoV vaccine and implementing appropriate infection control measures may control the continuing epidemic.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Protein folding in the cell.

            In the cell, as in vitro, the final conformation of a protein is determined by its amino-acid sequence. But whereas some isolated proteins can be denatured and refolded in vitro in the absence of other macromolecular cellular components, folding and assembly of polypeptides in vivo involves other proteins, many of which belong to families that have been highly conserved during evolution.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Role of the unfolded protein response regulator GRP78/BiP in development, cancer, and neurological disorders.

              GRP78/BiP is a major endoplasmic reticulum (ER) chaperone protein critical for protein quality control of the ER, as well as controlling the activation of the ER-transmembrane signaling molecules. Through creation of mouse models targeting the Grp78 allele, the function of GRP78 in development and disease has been investigated. These led to the discovery that GRP78 function is obligatory for early embryonic development. However, in adult animals, GRP78 is preferably required for cancer cell survival under pathologic conditions such as tumor progression and drug resistance. The discovery of surface localization of GRP78 in cancer cells reveals potential novel function, interaction with cell-surface receptors, and possible therapeutic implications. Mouse models also reveal that GRP78 controls maturation and secretion of neuronal factors for proper neural migration and offers neuroprotection.
                Bookmark

                Author and article information

                Contributors
                Journal
                Life Sci
                Life Sci
                Life Sciences
                Elsevier
                0024-3205
                1879-0631
                9 April 2019
                1 June 2019
                9 April 2019
                : 226
                : 156-163
                Affiliations
                Biophysics Department, Faculty of Science, Cairo University, Giza, Egypt
                Author notes
                [* ]Corresponding author. abdo@ 123456sci.cu.edu.eg
                Article
                S0024-3205(19)30272-3
                10.1016/j.lfs.2019.04.022
                7094232
                30978349
                075baa55-4647-4cd7-bf60-8202ef84f3ac
                © 2019 Elsevier Inc. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 4 March 2019
                : 1 April 2019
                : 9 April 2019
                Categories
                Article

                grp78,heat shock proteins,hsp70,stress,unfolded protein response,membrane receptors

                Comments

                Comment on this article