Identifying USPs regulating immune signals in

Engel, Élodie; Viargues, Perrine; Mortier, Magda; Taillebourg, Emmanuel; Couté, Yohann; Thevenon, Dominique; Fauvarque, Marie-Odile

doi:10.1186/preaccept-1588328929121802

Cited by 7 publications

(7 citation statements)

References 41 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A hundred DUBs have been identified in the human genome [ 15 , 16 ] and the Drosophila genome contains 41 DUB encoding genes, 34 of which having at least one human orthologue [ 17 ]. Genetic screens identified crucial DUBs involved in the regulation of apoptosis [ 18 ], of the Notch pathway [ 19 ] and of the innate immune response [ 20 ]. DUBs are categorized in five sub-families according to the structure of their catalytic domain: Ubiquitin C-terminal Hydrolases (UCH), Ubiquitin-Specific Proteases (USP), Machado-Joseph Disease Proteases (MJD), Otubain proteases (OTU) and JAB1/MPN/Mov34 Metalloenzymes (JAMM).…”

Section: Introductionmentioning

confidence: 99%

The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila

et al. 2015

Self Cite

View full text Add to dashboard Cite

Autophagy is a catabolic process that delivers cytoplasmic components to the lysosomes. Protein modification by ubiquitination is involved in this pathway: it regulates the stability of autophagy regulators such as BECLIN-1 and it also functions as a tag targeting specific substrates to autophagosomes. In order to identify deubiquitinating enzymes (DUBs) involved in autophagy, we have performed a genetic screen in the Drosophila larval fat body. This screen identified Uch-L3, Usp45, Usp12 and Ubpy. In this paper, we show that Ubpy loss of function results in the accumulation of autophagosomes due to a blockade of the autophagy flux. Furthermore, analysis by electron and confocal microscopy of Ubpy-depleted fat body cells revealed altered lysosomal morphology, indicating that Ubpy inactivation affects lysosomal maintenance and/or biogenesis. Lastly, we have shown that shRNA mediated inactivation of UBPY in HeLa cells affects autophagy in a different way: in UBPY-depleted HeLa cells autophagy is deregulated.

show abstract

Section: Introductionmentioning

confidence: 99%

The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…However, only a minority of them have been functionally characterized. The USPs are the biggest subfamily with more than 50 members 33 , with some of them known to regulate antiviral immune responses 28 , 34 , 35 . Previous studies have indicated that EV71 infection induces the up-regulation of USP19, which negatively regulates the antiviral type I interferon signalling by removing K-63 polyubiquitin chains from TRAF3 35 .…”

Section: Discussionmentioning

confidence: 99%

USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication

Peng

Zhang

et al. 2018

Sci Rep

View full text Add to dashboard Cite

Retinoic acid-inducible gene I-like receptor (RLR) is one of the most important pattern recognition receptors of the innate immune system that detects positive and/or negative stranded RNA viruses. Subsequently, it stimulates downstream transcription of interferon regulatory factor 3 (IRF3) and nuclear factor κB (NF-κB) inducing the production of interferons (IFNs) and inflammatory cytokines. Tumour necrosis factor receptor associated factor 6 (TRAF6) is a key protein involved in the RLR-mediated antiviral signalling pathway, recruiting additional proteins to form a multiprotein complex capable of activating the NF-κB inflammatory pathway. Despite TRAF6 playing an important role in regulating host immunity and viral infection, the deubiquitination of TRAF6 induced by viral infection remains elusive. In this study, we found that enterovirus 71 (EV71) infection attenuated the expression of Ubiquitin-specific protease 4 (USP4) in vitro and in vivo, while overexpression of USP4 significantly suppressed EV71 replication. Furthermore, it was found that EV71 infection reduced the RLR signalling pathway and enhanced the degradation of TRAF6. USP4 was also found to interact with TRAF6 and positively regulate the RLR-induced NF-κB signalling pathway, inhibiting the replication of EV71. Therefore, as a novel positive regulator of TRAF6, USP4 plays an essential role in EV71 infection by deubiquitinating K48-linked ubiquitin chains.

show abstract

“…The identified mutation in UPS36 gene is p.Arg631Gly. This gene is a known member of the ubiquitin specific protease family that regulates the immune signaling pathway [ 28 ]. The p.Arg338Cys mutation in SPN was also identified in our patients, and the influence of this gene can affect cellular defense responses and the regulation of the tumor necrosis factor (TNF) pathway [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genetic variations affecting osteoarthritis patients

et al. 2016

View full text Add to dashboard Cite

BackgroundOsteoarthritis (OA) is a progressive joint disease characterized by gradual degradation of extracellular matrix (ECM) components in the cartilage and bone. The ECM of cartilage is a highly specified structure that is mainly composed of type II collagen and provides tensile strength to the tissue via aggrecan and proteoglycans. However, changes in the ECM composition and structure can lead to loss of collagen type II and network integrity. Several risk factors have been correlated with OA including age, genetic predisposition, hereditary factors, obesity, mechanical injuries, and joint trauma. Certain genetic association studies have identified several genes associated with OA using genome-wide association studies (GWASs).ResultsWe identified several novel genetic variants affecting genes that function in several candidate causative pathways including immune responses, inflammatory and cartilage degradation such as SELP, SPN, and COL6A6.ConclusionsThe approach of whole-exome sequencing can be a promising method to identify genetic mutations that can influence the OA disease.

show abstract

Identifying USPs regulating immune signals in

Cited by 7 publications

References 41 publications

The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila

The Deubiquitinating Enzyme UBPY Is Required for Lysosomal Biogenesis and Productive Autophagy in Drosophila

USP4 positively regulates RLR-induced NF-κB activation by targeting TRAF6 for K48-linked deubiquitination and inhibits enterovirus 71 replication

Identification of novel genetic variations affecting osteoarthritis patients

Contact Info

Product

Resources

About