ERdj5, an Endoplasmic Reticulum (ER)-resident Protein Containing DnaJ and Thioredoxin Domains, Is Expressed in Secretory Cells or following ER Stress

Cunnea, Paula; Miranda‐Vizuete, Antonio; Bertoli, Gloria; Simmen, Thomas; Damdimopoulos, Anastasios; Hermann, Stefan; Leinonen, Saku; Huikko, Markku Pelto; Gustafsson, Jan Åke; Sitia, Roberto; Spyrou, Giannis

doi:10.1074/jbc.m206995200

Cited by 175 publications

(147 citation statements)

References 56 publications

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“…ERdj5 (DNAJC10/JPDI) is an ER-resident lumenal protein with a canonical C-terminal KDEL retrieval motif, a J domain, and four thioredoxin-like domains (Cunnea et al, 2003;Hosoda et al, 2003). Deletion of the J domain prevented interaction of ERdj5 with both BiP and misfolded SP-C, suggesting that association of ERdj5 with substrate was mediated by BiP.…”

Section: Discussionmentioning

confidence: 99%

“…vitro (Cunnea et al, 2003;Hosoda et al, 2003) may reflect the substrate specificity of ERdj5 or the requirement of a partner protein(s), such as BiP, for unfoldase activity. Alternatively, ERdj5 may act as a redox sensor to identify proteins with unpaired/mispaired cysteines and target them for elimination via ERAD.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, five HSP40 family members (DnaJ proteins) involved in modulation of HSP70 ATPase activity were also significantly induced (1.7ϳ4.3-fold; Table 1). Two recently identified DnaJ proteins, ERdj4 and ERdj5 (Shen et al, 2002;Cunnea et al, 2003), were especially noteworthy because these were among the most highly induced genes (3.4-to 4.3-fold) in response to expression of either SP-C ⌬exon4 or SP-C L188Q (Table 1). ERdj4 and ERdj5 contain eight and seven putative UPREs, respectively, within 2 kb of the transcription start site suggesting that they may be targets of XBP-1, a transcription factor involved in the regulation of ERAD.…”

Section: Microarray Analysis Reveals Candidate Genes Involved In Er Qmentioning

confidence: 99%

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ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C

Dong

Bridges

Apsley

et al. 2008

MBoC

142

171

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Mutations in the SFTPC gene associated with interstitial lung disease in human patients result in misfolding, endoplasmic reticulum (ER) retention, and degradation of the encoded surfactant protein C (SP-C) proprotein. In this study, genes specifically induced in response to transient expression of two disease-associated mutations were identified by microarray analyses. Immunoglobulin heavy chain binding protein (BiP) and two heat shock protein 40 family members, endoplasmic reticulum-localized DnaJ homologues ERdj4 and ERdj5, were significantly elevated and exhibited prolonged and specific association with the misfolded proprotein; in contrast, ERdj3 interacted with BiP, but it did not associate with either wild-type or mutant SP-C. Misfolded SP-C, ERdj4, and ERdj5 coprecipitated with p97/VCP indicating that the cochaperones remain associated with the misfolded proprotein until it is dislocated to the cytosol. Knockdown of ERdj4 and ERdj5 expression increased ER retention and inhibited degradation of misfolded SP-C, but it had little effect on the wild-type protein. Transient expression of ERdj4 and ERdj5 in X-box binding protein 1 ؊/؊ mouse embryonic fibroblasts substantially restored rapid degradation of mutant SP-C proprotein, whereas transfection of HPD mutants failed to rescue SP-C endoplasmic reticulum-associated protein degradation. ERdj4 and ERdj5 promote turnover of misfolded SP-C and this activity is dependent on their ability to stimulate BiP ATPase activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Microarray Analysis Reveals Candidate Genes Involved In Er Qmentioning

confidence: 99%

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ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C

Dong

Bridges

Apsley

et al. 2008

MBoC

142

171

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“…14,15 ERdj5 plays central roles in the degradation of misfolded proteins via its four thioredoxinlike domains (TRX) that contribute to reductase activity. [16][17][18] As mentioned above, organization of ERdjs is different in mammals, yeast and plants ( Fig. 1).…”

Section: Gene Organization Of Erdjs In Different Organismsmentioning

confidence: 99%

Emerging features of ER resident J-proteins in plants

Ohta¹,

Takaiwa²

2014

Plant Signaling & Behavior

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“…71,73,74 Up to now, a few more substrates were detected such as the low-density lipoprotein receptor (LDLR), where ERdj5 aids in efficient folding and not LDLR degradation. 74 Future studies will reveal more insight into the DNJ-27 interaction network and its substrates for its role as thioreductase and as J-protein in context of diverse neurodegenerative disease models and aging.…”

Section: The Crucial Role Of Pdi's and Ero-1 To Maintain Er Homeostasmentioning

confidence: 99%

Interplay between redox and protein homeostasis

Feleciano

Arnsburg

Kirstein

2016

Worm

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The subcellular compartments of eukaryotic cells are characterized by different redox environments. Whereas the cytosol, nucleus and mitochondria are more reducing, the endoplasmic reticulum represents a more oxidizing environment. As the redox level controls the formation of intra-and inter-molecular disulfide bonds, the folding of proteins is tightly linked to its environment. The proteostasis network of each compartment needs to be adapted to the compartmental redox properties. In addition to chaperones, also members of the thioredoxin superfamily can influence the folding of proteins by regulation of cysteine reduction/oxidation. This review will focus on thioredoxin superfamily members and chaperones of C. elegans, which play an important role at the interface between redox and protein homeostasis. Additionally, this review will highlight recent methodological developments on in vivo and in vitro assessment of the redox state and their application to provide insights into the high complexity of redox and proteostasis networks of C. elegans.

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ERdj5, an Endoplasmic Reticulum (ER)-resident Protein Containing DnaJ and Thioredoxin Domains, Is Expressed in Secretory Cells or following ER Stress

Abstract: A complex array of chaperones and enzymes reside in the endoplasmic reticulum (ER) to assist the folding and assembly of and the disulfide bond formation in nascent secretory proteins. Here we characterize a novel human putative ER co-chaperone (ERdj5)

Cited by 175 publications

References 56 publications

ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C

ERdj4 and ERdj5 Are Required for Endoplasmic Reticulum-associated Protein Degradation of Misfolded Surfactant Protein C

Emerging features of ER resident J-proteins in plants

Interplay between redox and protein homeostasis

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