Role of the Endoplasmic Reticulum-associated Degradation (ERAD) Pathway in Degradation of Hepatitis C Virus Envelope Proteins and Production of Virus Particles

Saeed, Mohsan; Suzuki, Ritsuro; Watanabe, Noriyuki; Masaki, Takahiro; Tomonaga, Mitsunori; Muhammad, Amir; Kato, Takanobu; Matsuura, Yoshiharu; Watanabe, Haruo; Wakita, Takaji; Suzuki, Tetsuro

doi:10.1074/jbc.m111.259085

Cited by 81 publications

(92 citation statements)

References 27 publications

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“…Flaviviruses, including West Nile virus, are known to replicate in close association with ER-derived membrane structures and to induce ER stress (Brinton, 2014), and some components of the ERAD pathway have been shown to play a role in flavivirus replication (Krishnan et al, 2008; Li et al, 2014; Saeed et al, 2011; Sharma et al, 2014) as well as the replication of other viruses (Bennett et al, 2013; Bernasconi et al, 2012; Reggiori et al, 2010; van den Boomen et al, 2014). It is known that WNV replication induces cell death; however, how exactly WNV replication triggers this is unknown.…”

Section: Discussionmentioning

confidence: 99%

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death

Dang

Wu³

et al. 2015

Cell Reports

198

164

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Summary West Nile virus (WNV) causes an acute neurological infection attended by massive neuronal cell death. However, the mechanism(s) behind the virus-induced cell death is poorly understood. Using a library containing 77,406 sgRNAs targeting 20,121 genes, we performed a genome-wide screen followed by a second screen with a sub-library. Among the genes identified, seven genes, EMC2, EMC3, SEL1L, DERL2, UBE2G2, UBE2J1, and HRD1, stood out as having the strongest phenotype, whose knockout conferred strong protection against WNV-induced cell death with two different WNV strains and in three cell lines. Interestingly, knockout of these genes did not block WNV replication. Thus, these appear to be essential genes that link WNV replication to downstream cell death pathway(s). In addition, the fact that all of these genes belong to the endoplasmic reticulum-associated protein degradation (ERAD) pathway suggests that this might be the primary driver of WNV-induced cell death.

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Section: Discussionmentioning

confidence: 99%

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death

Dang

Wu³

et al. 2015

Cell Reports

198

164

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“…Although much of the literature supports the role of mannose trimming from misfolded proteins as critical to their recognition for ERAD, one cannot overlook the fact that much of the ERAD quality control machinery, including EDEM1, OS-9, XTP3-B, and SEL1L, are themselves N-glycosylated. Because the removal of mannose units from their N-glycans is required for ERAD (24,57), one should consider in future studies that treatment with KIF might actually function by inhibiting critical ERAD associations with SEL1L (24,48,49).…”

Section: Discussionmentioning

confidence: 99%

“…Acceleration of ERAD by Recombinant MAN1B1 Catalytic Mutants Is Sensitive to Kifunensine and Mediated by the Proteasome-The capacity of KIF to disrupt ERAD is thought to involve either the inhibition of essential mannosidase activity or the prevention of important downstream lectin-ligand interactions (48,49). Because KIF failed to prevent the co-immunoprecipitation of endogenous MAN1B1 and NHK (Fig.…”

Section: Neither the Catalytic Activity Nor The Luminal Catalytic Dommentioning

confidence: 99%

A Golgi-localized Mannosidase (MAN1B1) Plays a Non-enzymatic Gatekeeper Role in Protein Biosynthetic Quality Control

Iannotti

Figard

Sokac

et al. 2014

Journal of Biological Chemistry

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Background:The capacity of Golgi-localized MAN1B1 to promote ERAD was investigated. Results: The MAN1B1 catalytic domain is dispensable for ERAD, which helped identify an important conserved, non-enzymatic decapeptide sequence within the luminal stem. Conclusion:The tempo-spatial expansion of quality control in the secretory pathway includes evolutionary gain-of-function for MAN1B1. Significance: Evolutionary distinctions can exist in how quality control systems operate.

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“…The luminal N-terminal domain of SEL1L contains eleven tetratricopeptide repeats (TPR) and five possible N-linked glycosylation sites that appear to work in concert to recruit the OS-9 or XTP3-B-substrate complex to the ERAD complex and to pass the substrate along to the dislocation and ubiquitination machinery. EDEM1 and EDEM3 also appear to serve this role as they both bind ERAD substrates and interact with SEL1L in a glycan dependent manner 66, 67 . ERAD substrates are prepared for dislocation by associated factors such as ERdj5 and BiP for EDEM1, and possibly GRP94 for OS-9 65, 68 .…”

Section: Extrinsic Influence Of N-glycans On Glycoproteostasismentioning

confidence: 99%

The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis

et al. 2014

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Proteins that traffic through the eukaryotic secretory pathway are commonly modified with N-linked carbohydrates. These bulky amphipathic modifications at asparagines intrinsically enhance solubility and folding energetics through carbohydrate-protein interactions. N-linked glycans can also extrinsically enhance glycoprotein folding by utilizing the glycoprotein homeostasis or “glycoproteostasis” network, comprising numerous glycan binding and/or modification enzymes or proteins that synthesize, transfer, sculpt and utilize N-linked glycans to direct folding vs. degradation, and trafficking of nascent N-glycoproteins through the cellular secretory pathway. If protein maturation is perturbed by misfolding and/or aggregation, stress pathways are often activated that result in transcriptional remodeling of the secretory pathway, in an attempt to alleviate the insult(s). The inability to achieve glycoproteostasis is linked to several pathologies, including amyloidoses, cystic fibrosis, and lysosomal storage diseases. Recent progress on genetic and pharmacologic adaptation of the glycoproteostasis network provides hope that drugs can be developed for these maladies in the near future.

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Role of the Endoplasmic Reticulum-associated Degradation (ERAD) Pathway in Degradation of Hepatitis C Virus Envelope Proteins and Production of Virus Particles

Cited by 81 publications

References 27 publications

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death

A CRISPR-Based Screen Identifies Genes Essential for West-Nile-Virus-Induced Cell Death

A Golgi-localized Mannosidase (MAN1B1) Plays a Non-enzymatic Gatekeeper Role in Protein Biosynthetic Quality Control

The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis

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