SARS-CoV-2 Switches ‘on’ MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression

Goel, Swati; Sharif-Askari, Fatemeh Saheb; Askari, Narjes Saheb Sharif; Madkhana, Bushra; Alwaa, Ahmad Munzer; Mahboub, Bassam; Zakeri, Adel M; Ratemi, Elaref; Hamoudi, Rifat; Hamid, Qutayba; Halwani, Rabih

doi:10.3389/fphar.2021.631879

Cited by 62 publications

(61 citation statements)

References 63 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…DUSP1/6 were reported to serve as crucial regulators in PM2.5 exposure and COVID-19 infection or to induce proinflammatory immune responses in lung epithelial or endothelial cells through regulation of MAPK signals and NF-κB signaling. 209 – 212 Vattakuzhi et al reported that DUSP1 attenuated MAPK signaling, whereas its deficiency enhanced inflammatory osteolysis, which may be associated with osteolytic destruction. 213 DUSP1/6 were both reported to have a function in cardiovascular diseases through inactivation of MAPK signaling.…”

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage. On the other hand, inflammation can also initiate tissue damage repair and maintain normal tissue function by resolving injury and restoring homeostasis. These opposing functions emphasize the significance of accurate regulation of inflammatory homeostasis to ameliorate inflammation-related diseases. Potential mechanisms involve protein phosphorylation modifications by kinases and phosphatases, which have a crucial role in inflammatory homeostasis. The mechanisms by which many kinases resolve inflammation have been well reviewed, whereas a systematic summary of the functions of protein phosphatases in regulating inflammatory homeostasis is lacking. The molecular knowledge of protein phosphatases, and especially the unique biochemical traits of each family member, will be of critical importance for developing drugs that target phosphatases. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of all protein phosphatases in inflammation-related diseases, as well as their potential inhibitors or activators that can be used in therapeutic interventions in preclinical or clinical trials. We provide an integrated perspective on the current understanding of all the protein phosphatases associated with inflammation-related diseases, with the aim of facilitating the development of drugs that target protein phosphatases for the treatment of inflammation-related diseases.

show abstract

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…TLR3 and TLR4 stimulation results in NF-kB activation [174]. Of note, SARS-CoV-2 infection results in higher NF-kB pathway activation [213]. Notably, BRD4 control of innate immunity largely relies on BRD4 regulation of canonical NF-kB pathway, associated with transcription factor RELA.…”

Section: Sars-cov-2 Induced Immune Response and Bet Proteinsmentioning

confidence: 99%

Relevance of BET Family Proteins in SARS-CoV-2 Infection

Lara-Ureña

García-Domínguez

2021

Biomolecules

View full text Add to dashboard Cite

The recent pandemic we are experiencing caused by the coronavirus disease 2019 (COVID-19) has put the world’s population on the rack, with more than 191 million cases and more than 4.1 million deaths confirmed to date. This disease is caused by a new type of coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A massive proteomic analysis has revealed that one of the structural proteins of the virus, the E protein, interacts with BRD2 and BRD4 proteins of the Bromodomain and Extra Terminal domain (BET) family of proteins. BETs are essential to cell cycle progression, inflammation and immune response and have also been strongly associated with infection by different types of viruses. The fundamental role BET proteins play in transcription makes them appropriate targets for the propagation strategies of some viruses. Recognition of histone acetylation by BET bromodomains is essential for transcription control. The development of drugs mimicking acetyl groups, and thereby able to displace BET proteins from chromatin, has boosted interest on BETs as attractive targets for therapeutic intervention. The success of these drugs against a variety of diseases in cellular and animal models has been recently enlarged with promising results from SARS-CoV-2 infection studies.

show abstract

“… 1 , 2 Viral antigens are among the cellular stimuli capable to activate NF‐kB, including those of the respiratory virus subfamily Coronavirus. 3 A sustained NF‐κB signaling has been observed in human airway epithelial cells infected with SARS‐CoV‐2, possibly by the modified expression of regulatory proteins such as dual‐specificity phosphatases 1 and 5, 4 and PARPs 5 involved in apoptotic pathway modulation. 6 Again, this transcription factor has been speculated to represent one of the therapeutic targets in this infection along with other cellular stress and pro‐inflammatory pathways.…”

Section: Introductionmentioning

confidence: 99%

“…A characteristic cellular response to NF‐kB activation is the transcriptional activation of inflammatory genes 1,4 . This suggests the possibility that NF‐kB hyperactivation in SARS‐CoV‐2 infected cells may contribute to investigate cellular stress by the abnormal expression of inflammatory genes.…”

Section: Introductionmentioning

confidence: 99%

“…7 A characteristic cellular response to NF-kB activation is the transcriptional activation of inflammatory genes. 1,4 This suggests the possibility that NF-kB hyperactivation in SARS-CoV-2 infected cells may contribute to investigate cellular stress by the abnormal expression of inflammatory genes. At the same time, an increased burden of NF-kB activation is expected to play a main role in promoting the inflammatory comorbidity of COVID-19.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Endoplasmic reticulum stress and NF‐kB activation in SARS‐CoV‐2 infected cells and their response to antiviral therapy

et al. 2021

View full text Add to dashboard Cite

Unfolded protein response (UPR) and endoplasmic reticulum (ER) stress are aspects of SARS-CoV-2-host cell interaction with proposed role in the cytopathic and inflammatory pathogenesis of this viral infection. The role of the NF-kB pathway in these cellular processes remains poorly characterized.When investigated in VERO-E6 cells, SARS-CoV-2 infection was found to markedly stimulate NF-kB protein expression and activity. NF-kB activation occurs early in the infection process (6 hpi) and it is associated with increased MAPK signaling and expression of the UPR inducer IRE-1α. These signal transduction processes characterize the cellular stress response to the virus promoting a pro-inflammatory environment and caspase activation in the host cell. Inhibition of viral replication by the viral protease inhibitor Nelfinavir reverts all these molecular changes also stimulating c-Jun expression, a key component of the JNK/AP-1 pathway with important role in the IRE-1αmediated transcriptional regulation of stress response genes with antiinflammatory and cytoprotection function. The present study demonstrates that UPR signaling and its interaction with cellular MAPKs and the NF-kB activity are important aspects of SARS-CoV-2-host cell interaction that deserve further investigation to identify more efficient therapies for this viral infection.

show abstract

SARS-CoV-2 Switches ‘on’ MAPK and NFκB Signaling via the Reduction of Nuclear DUSP1 and DUSP5 Expression

Cited by 62 publications

References 63 publications

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Relevance of BET Family Proteins in SARS-CoV-2 Infection

Endoplasmic reticulum stress and NF‐kB activation in SARS‐CoV‐2 infected cells and their response to antiviral therapy

Contact Info

Product

Resources

About