Characterization of the proteasome interaction with the Sec61 channel in the endoplasmic reticulum

Ng, Waiyan; Sergeyenko, Tatiana V; Zeng, Naiyan; Brown, Jonathon D.; Römisch, Karin

doi:10.1242/jcs.03351

Cited by 49 publications

(58 citation statements)

References 45 publications

(134 reference statements)

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“…Although the identities of the components that comprise the retrotranslocation channel remain unclear, Sec61 complex and Derlin-1 are possible candidates (Knop et al 1996;Pilon et al 1997;Willer et al 2008;Schafer and Wolf 2009). Sec61 complex has been reported to interact with several ERAD substrates and ERAD machineries including proteasome, TRAP complex, SPP (signal peptide peptidase), PDI, and BAP31 Pilon et al 1997;Loureiro et al 2006;Nagasawa et al 2007;Ng et al 2007;Wang et al 2008;Lee et al 2010). Derlin-1 was initially reported to be important for the extraction of MHC class I molecules from the ER membrane in cytomegalovirus-infected cells (Lilley and Ploegh 2004;Ye et al 2004).…”

Section: Retrotranslocation and Degradationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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The endoplasmic reticulum (ER) uses an elaborate surveillance system called the ER quality control (ERQC) system. The ERQC facilitates folding and modification of secretory and membrane proteins and eliminates terminally misfolded polypeptides through ER-associated degradation (ERAD) or autophagic degradation. This mechanism of ER protein surveillance is closely linked to redox and calcium homeostasis in the ER, whose balance is presumed to be regulated by a specific cellular compartment. The potential to modulate proteostasis and metabolism with chemical compounds or targeted siRNAs may offer an ideal option for the treatment of disease.

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Section: Retrotranslocation and Degradationmentioning

confidence: 99%

Protein Folding and Quality Control in the ER

Araki

Nagata

2011

Cold Spring Harbor Perspectives in Biology

317

285

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“…Transport of proteins from the ER back to the cytoplasm occurs during ERassociated degradation (ERAD), where ER proteins prone for degradation are transported through the translocon back to the cytoplasm for degradation by the proteasome [28]. In yeast, Sec63p and BiP co-precipitate with ER-associated proteasomes and mutations in Sec63p or BiP affect degradation of unfolded proteins in the ER [29,30]. BiP recognizes hydrophobic regions of misfolded or partially assembled proteins and promotes ER retention and protein folding [31].…”

Section: Sec63mentioning

confidence: 99%

Congenital disorders of glycosylation in hepatology: The example of polycystic liver disease

Janssen¹,

Waanders²,

Woudenberg³

et al. 2010

Journal of Hepatology

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Autosomal dominant polycystic liver disease (PCLD) is a rare progressive disorder characterized by an increased liver volume due to many (>20) fluid-filled cysts of biliary origin. Disease causing mutations in PRKCSH or SEC63 are found in approximately 25% of the PCLD patients. Both gene products function in the endoplasmic reticulum, however, the molecular mechanism behind cyst formation remains to be elucidated. As part of the translocon complex, SEC63 plays a role in protein import into the ER and is implicated in the export of unfolded proteins to the cytoplasm during ER-associated degradation (ERAD). PRKCSH codes for the beta-subunit of glucosidase II (hepatocystin), which cleaves two glucose residues of Glc(3)Man(9)GlcNAc(2) N-glycans on proteins. Hepatocystin is thereby directly involved in the protein folding process by regulating protein binding to calnexin/calreticulin in the ER. A separate group of genetic diseases affecting protein N-glycosylation in the ER is formed by the congenital disorders of glycosylation (CDG). In distinct subtypes of this autosomal recessive multisystem disease specific liver symptoms have been reported that overlap with PCLD. Recent research revealed novel insights in PCLD disease pathology such as the absence of hepatocystin from cyst epithelia indicating a two-hit model for PCLD cystogenesis. This opens the way to speculate about a recessive mechanism for PCLD pathophysiology and shared molecular pathways between CDG and PCLD. In this review we will discuss the clinical-genetic features of PCLD and CDG as well as their biochemical pathways with the aim to identify novel directions of research into cystogenesis.

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“…It has been shown that the 26S proteasome disassembles in an ATP-dependent catalytic cycle, leading to 19S RP subcomplexes and free 26S protease regulatory subunit 5a (Babbitt et al, 2005). In contrast, 19S RPs are able to interact with Sec61 at the ER membrane (Ng et al, 2007). Wahlman et al (2007) demonstrated that ATP, the 19S RP, the ER luminal chaperone PDI, and Derlin-1 are sufficient to retrotranslocate a soluble ERAD substrate in vitro (Wahlman et al, 2007).…”

Section: Downloaded Frommentioning

confidence: 99%

Derlin-1 and p97/Valosin-Containing Protein Mediate the Endoplasmic Reticulum-Associated Degradation of Human V2 Vasopressin Receptors

Schwieger

Lautz²,

Krause³

et al. 2007

Mol Pharmacol

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The endoplasmic reticulum-associated degradation (ERAD), the main quality control pathway of the cell, is crucial for the elimination of unfolded or misfolded proteins. Several diseases are associated with the retention of misfolded proteins in the early secretory pathway. Among them is X-linked nephrogenic diabetes insipidus, caused by mutations in the gene encoding the V2 vasopressin receptor (V2R). We studied the degradation pathways of three intracellularly retained V2R mutants with different misfolded domains in human embryonic kidney 293 cells. At steady state, the wild-type V2R and the complexglycosylated mutant G201D were partially located in lysosomes, whereas core-glycosylated mutants L62P and V226E were excluded from this compartment. In pulse-chase experiments, proteasomal inhibition stabilized the nonglycosylated and core-glycosylated forms of all studied receptors. In addition, all mutants and the wild-type receptor were found to be polyubiquitinylated. Nonglycosylated and core-glycosylated receptor forms were located in cytosolic and membrane fractions, respectively, confirming the deglycosylation and retrotranslocation of ERAD substrates to the cytosol. Distinct Derlin-1-dependent and -independent ERAD pathways have been proposed for proteins with different misfolded domains (cytosolic, extracellular, and membrane) in yeast. Here, we show for the first time that V2R mutants with different misfolded domains are able to coprecipitate the ERAD components p97/valosincontaining protein, Derlin-1 and the 26S proteasome regulatory subunit 7. Our results demonstrate the presence of a Derlin-1-mediated ERAD pathway degrading wild-type and diseasecausing V2R mutants with different misfolded domains in a mammalian system.

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Characterization of the proteasome interaction with the Sec61 channel in the endoplasmic reticulum

Cited by 49 publications

References 45 publications

Protein Folding and Quality Control in the ER

Protein Folding and Quality Control in the ER

Congenital disorders of glycosylation in hepatology: The example of polycystic liver disease

Derlin-1 and p97/Valosin-Containing Protein Mediate the Endoplasmic Reticulum-Associated Degradation of Human V2 Vasopressin Receptors

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