<scp>GRP</scp>78 protects a disintegrin and metalloprotease 17 against protein‐disulfide isomerase A6 catalyzed inactivation

Schäfer, Miriam R.; Granato, Daniela Campos; Krossa, Sebastian; Bartels, Anne-Kathrin; Yokoo, Sami; Düsterhöft, Stefan; Koudelka, Tomas; Scheidig, Axel J.; Tholey, Andreas; Leme, Adriana Franco Paes; Grötzinger, Joachim; Lorenzen, Inken

doi:10.1002/1873-3468.12858

Cited by 10 publications

(6 citation statements)

References 80 publications

(139 reference statements)

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“…Androgens have also been reported to upregulate GRP78 (156,157) and this could be a further contributing factor to the increased risk of COVID-19 in males. Other relevant functions of cell surface GRP78 are its ability to bind and stabilize ADAM17 (158) and also bind to tissue factor and regulate the initiation of coagulation (159).…”

Section: Glucose-regulated Protein 78 (Grp78)mentioning

confidence: 99%

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

et al. 2020

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The pandemic of COVID-19, caused by the coronavirus, SARS-CoV-2, has had a global impact not seen for an infectious disease for over a century. This acute pandemic has spread from the East and has been overlaid onto a slow pandemic of metabolic diseases of obesity and diabetes consequent from the increasing adoption of a Western-lifestyle characterized by excess calorie consumption with limited physical activity. It has become clear that these conditions predispose individuals to a more severe COVID-19 with increased morbidity and mortality. There are many features of diabetes and obesity that may accentuate the clinical response to SARS-CoV-2 infection: including an impaired immune response, an atherothrombotic state, accumulation of advanced glycation end products and a chronic inflammatory state. These could prime an exaggerated cytokine response to viral infection, predisposing to the cytokine storm that triggers progression to septic shock, acute respiratory distress syndrome, and multi-organ failure. Infection leads to an inflammatory response and tissue damage resulting in increased metabolic activity and an associated increase in the mechanisms by which cells ingest and degrade tissue debris and foreign materials. It is becoming clear that viruses have acquired an ability to exploit these mechanisms to invade cells and facilitate their own life-cycle. In obesity and diabetes these mechanisms are chronically activated due to the deteriorating metabolic state and this may provide an increased opportunity for a more profound and sustained viral infection.

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Section: Glucose-regulated Protein 78 (Grp78)mentioning

confidence: 99%

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

et al. 2020

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“…Cells irradiated by radiation will release damageassociated molecular patterns (DAMPs) by activating GRP78, and tumor cells will be devoured by antigen-presenting cells. At the same time, cytotoxic T cells will get information and promote the destruction of tumor cells (45)(46)(47)(48)(49). However, its overexpression on proliferating and quiescent cancer cells and tumor-related endothelial cells is conducive to escape from chemotherapy and other therapeutic methods.…”

Section: Participation In Immune Activation and Immunosuppressionmentioning

confidence: 99%

Targeting the GRP78 Pathway for Cancer Therapy

Luo

Zhu

2020

Front. Med.

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The 78-kDa glucose-regulated protein (GRP78) plays an important part in maintaining protein stability, regulating protein folding, and inducing apoptosis autophagy, which is considered as a powerful protein. Meanwhile, it also plays a role in ensuring the normal function of organs. In recent years, more and more researches have been carried out on the targeted therapy of GRP78, mainly focusing on its relevant role in tumor and its role as a major modulator and modulator of subordinate pathways. The ability of GRP78 to respond to endoplasmic reticulum stress (ERS) determines whether tumor cells survive and whether the changes in expression level of GRP78 regulated by endoplasmic reticulum (ER) caused by various factors will directly or indirectly affect cell proliferation, apoptosis, and injury, or reduce the body's defense ability, or have protective effects on various organs.

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“…These moderate affinities might be required for transient interactions with a fast release upon catalysis. Noteworthy, they are in the same order of magnitude as the affinity between MPD and GRP78, which protects the opMPD from the isomerization catalyzed by the PDIs 42 . Extracellular PDIA1, PDIA3, and PDIA6 share overlapping and complementary functions as shown for the activation of integrins during coagulation 34 , 36 – 38 .…”

Section: Resultsmentioning

confidence: 99%

Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17

Krossa

Scheidig

Grötzinger

et al. 2018

Sci Rep

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A Disintegrin and Metalloprotease 17 (ADAM17) can cause the fast release of growth factors and inflammatory mediators from the cell surface. Its activity has to be turned on which occurs by various stimuli. The active form can be inactivated by a structural change in its ectodomain, related to the pattern of the formed disulphide bridges. The switch-off is executed by protein disulfide isomerases (PDIs) that catalyze an isomerization of two disulfide bridges and thereby cause a disulfide switch. We demonstrate that the integrity of the CGHC-motif within the active site of PDIs is indispensable. In particular, no major variation is apparent in the activities of the two catalytic domains of PDIA6. The affinities between PDIA1, PDIA3, PDIA6 and the targeted domain of ADAM17 are all in the nanomolar range and display no significant differences. The redundancy between PDIs and their disulfide switch activity in ectodomains of transmembrane proteins found in vitro appears to be a basic characteristic. However, different PDIs might be required in vivo for disulfide switches in different tissues and under different cellular and physiological situations.

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GRP78 protects a disintegrin and metalloprotease 17 against protein‐disulfide isomerase A6 catalyzed inactivation

Cited by 10 publications

References 80 publications

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

Obesity, Diabetes and COVID-19: An Infectious Disease Spreading From the East Collides With the Consequences of an Unhealthy Western Lifestyle

Targeting the GRP78 Pathway for Cancer Therapy

Redundancy of protein disulfide isomerases in the catalysis of the inactivating disulfide switch in A Disintegrin and Metalloprotease 17

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