Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination

Budroni, Valentina; Versteeg, Gijs A.

doi:10.3390/v13040584

Cited by 10 publications

(7 citation statements)

References 405 publications

(663 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The levels of transcripts encoding E3 ligases such as Cbl-b and ITCH are reduced in the brains of patients with MS, but their levels increase during treatment with IFN, indicating that Cbl-b and ITCH are involved in MS pathogenesis [ 81 , 82 ]. Therefore, molecular targets of the UPS should be further identified; this could provide more insights into the molecular pathogenesis of MS as well as promote the identification of new drug targets.…”

Section: Therapeutic Targets In Upsmentioning

confidence: 99%

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Yadav

Lee

Puranik

et al. 2022

Cells

View full text Add to dashboard Cite

Multiple sclerosis (MS) is an autoimmune, neurodegenerative disease associated with the central nervous system (CNS). Autoimmunity is caused by an abnormal immune response to self-antigens, which results in chronic inflammation and tissue death. Ubiquitination is a post-translational modification in which ubiquitin molecules are attached to proteins by ubiquitinating enzymes, and then the modified proteins are degraded by the proteasome system. In addition to regulating proteasomal degradation of proteins, ubiquitination also regulates other cellular functions that are independent of proteasomal degradation. It plays a vital role in intracellular protein turnover and immune signaling and responses. The ubiquitin–proteasome system (UPS) is primarily responsible for the nonlysosomal proteolysis of intracellular proteins. The 26S proteasome is a multicatalytic adenosine-triphosphate-dependent protease that recognizes ubiquitin covalently attached to particular proteins and targets them for degradation. Damaged, oxidized, or misfolded proteins, as well as regulatory proteins that govern many essential cellular functions, are removed by this degradation pathway. When this system is affected, cellular homeostasis is altered, resulting in the induction of a range of diseases. This review discusses the biochemistry and molecular biology of the UPS, including its role in the development of MS and proteinopathies. Potential therapies and targets involving the UPS are also addressed.

show abstract

Section: Therapeutic Targets In Upsmentioning

confidence: 99%

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Yadav

Lee

Puranik

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…Ubiquitination is a common post-translational modification involved in numerous aspects of protein function, such as degradation, localization and protein-protein interactions (21). Deubiquitination is the reverse process mediated by deubiquitinating enzymes (DUBs), that serve a key role in biological activities, such as inflammation, signal transduction and the immune response (22,23). Ubiquitin-specific peptidase (USP)25 is a key deubiquitylase belonging to the USP superfamily that is primarily involved in inflammation and the immune response (24,25).…”

Section: Downregulation Of Deubiquitinating Enzyme Usp25mentioning

confidence: 99%

Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium

Chang

Tan

et al. 2022

Mol Med Rep

View full text Add to dashboard Cite

Ubiquitin-specific peptidase 25 (USP25) is a key deubiquitylase belonging to the USP superfamily that is primarily involved in inflammation and the immune response. Thymic stromal lymphopoietin (TSLP) is an epithelial-derived cytokine that is regarded as the master switch that initiates and maintains the type 2 immune response in allergic rhinitis (AR). However, the molecular mechanisms by which USP25 regulates TSLP signaling in the nasal epithelium in AR remain unclear. The present study assessed the protein expression levels of USP25 in the nasal epithelium of patients with AR. Moreover, USP25 knockout (KO) and wild-type (WT) mice were treated with ovalbumin (OVA) to establish a model of AR. The results of western blotting and immunohistochemistry in the present study demonstrated that the protein expression levels of USP25 were significantly decreased in the nasal mucosa of patients with AR and AR mice, whereas the protein expression levels of TSLP were significantly increased. Allergic inflammation was more severe in USP25 KO mice compared with WT mice exposed to OVA, as demonstrated by increased nose scratching and sneezing, increased eosinophil infiltration, goblet cell hyperplasia and enhanced T helper type 2 (Th2) cytokine production. The results of in vitro experiments demonstrated that silencing or overexpression of USP25 decreased or increased TNF receptor-associated factor 3 (TRAF3) protein expression levels, respectively, in human nasal epithelial cells, whereas TSLP protein expression levels were negatively associated with the expression of USP25 and TRAF3. In summary, USP25 downregulation enhanced TSLP signaling in the nasal mucosal epithelium via decreased TRAF3 expression, thereby exacerbating inflammation in AR. Therefore, USP25 may act as a novel therapeutic target in AR.

show abstract

“…The hemagglutinin of influenza A virus induces degradation of IFNAR by casein kinase 1α and poly(ADP‐ribose) polymerase 1 69–71 . The activation of p38 kinase triggers a series of phosphorylation cascades within the IFNAR1 chain, resulting in IFNAR1 ubiquitination and promoting the lysosomal degradation of IFNAR1 72,73 . Fat accumulation in HCV‐infected cells induces an ER stress‐mediated autophagy response and downregulates IFNAR1 in the lysosome 74,75 (Figure 2d).…”

Section: Autophagy‐regulated Innate Antiviral Immunitymentioning

confidence: 99%

Regulation of innate immune signaling pathways by autophagy in dengue virus infection

Wan

Lee

et al. 2021

IUBMB Life

View full text Add to dashboard Cite

Autophagy is not only an intracellular recycling degradation system that maintains cellular homeostasis but is also a component of innate immunity that contributes to host defense against viral infection. The viral components as well as viral particles trapped in autophagosomes can be delivered to lysosomes for degradation. Abundant evidence indicates that dengue virus (DENV) has evolved the potent ability to hijack or subvert autophagy process for escaping host immunity and promoting viral replication. Moreover, autophagy is often required to deliver viral components to pattern recognition receptors signaling for interferon (IFN)‐mediated viral elimination. Hence, this review summarizes DENV‐induced autophagy, which exhibits dual effects on proviral activity of promoting replication and antiviral activity to eliminating viral particles.

show abstract

Negative Regulation of the Innate Immune Response through Proteasomal Degradation and Deubiquitination

Cited by 10 publications

References 405 publications

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Modulating the Ubiquitin–Proteasome System: A Therapeutic Strategy for Autoimmune Diseases

Downregulation of deubiquitinating enzyme USP25 promotes the development of allergic rhinitis by enhancing TSLP signaling in the nasal epithelium

Regulation of innate immune signaling pathways by autophagy in dengue virus infection

Contact Info

Product

Resources

About