HEDJ, an Hsp40 Co-chaperone Localized to the Endoplasmic Reticulum of Human Cells

Yu, Meng‐Fei; Haslam, Robert H. A.; Haslam, David B.

doi:10.1074/jbc.m000739200

Cited by 101 publications

(119 citation statements)

References 35 publications

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“…ERdj3 was originally identified as a cochaperone (Yu et al, 2000;Shen and Hendershot, 2005). However, the characteristics of the ERdj3 primary amino acid sequence reveal that it may have dual roles.…”

Section: Erdj3 May Have Dual Functions During Neural Developmentmentioning

confidence: 99%

“…Among these fragments, eight clones contained DNA sequences corresponding to the C-terminal domain of ERdj3 (Fig. 4C), a protein with a signal sequence and reported previously to be an ER-resident cochaperone (Yu et al, 2000). To confirm the association of PRTG with ERdj3 and to delineate the interaction domains involved in the interaction of PRTG with ERdj3, a series of PRTG deletion mutants were constructed, and their interaction with the C-terminal region of ERdj3 was evaluated by yeast two-hybrid assay.…”

Section: Erdj3 As a Ligand For Prtgmentioning

confidence: 99%

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Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Wong¹,

Wang

et al. 2010

J. Neurosci.

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Many Ig superfamily members are expressed in the developing nervous system, but the functions of these molecules during neurogenesis are not all clear. Here, we explore the expression and function of one of members of this superfamily, protogenin (PRTG), in the developing nervous system. Expression of PRTG protein is strong in the neural tube of mouse embryos between embryonic days 7.75 and 9.5 but disappears after embryonic day 10.5 when the neural progenitor marker nestin expresses prominently. Perturbation of PRTG activity in P19 embryonal carcinoma cells and in chick embryos, by either RNA interference or a dominant-negative PRTG mutant, increases neuronal differentiation. Using yeast two-hybrid screening and an in situ binding assay, we were able to identify ERdj3 (a stress-inducible endoplasmic reticulum DnaJ homolog) as a putative PRTG ligand. Addition of purified ERdj3 protein into the P19 differentiation assay reduced neurogenesis. This effect was blocked by addition of either a neutralizing antibody against PRTG or purified PRTG ectodomain protein, indicating that the effect of ERdj3 on neurogenesis is mediated through PRTG. Forced expression of ERdj3 in the chick neural tube also impairs neuronal differentiation. Together, these results suggest that expression of PRTG defines a stage between pluripotent epiblasts and committed neural progenitors, and its signaling plays a critical role in suppressing premature neuronal differentiation during early neural development.

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Section: Erdj3 May Have Dual Functions During Neural Developmentmentioning

confidence: 99%

Section: Erdj3 As a Ligand For Prtgmentioning

confidence: 99%

Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Wong¹,

Wang

et al. 2010

J. Neurosci.

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“…In fact, we reported that various NSAIDs induced the expression of glucoseregulated protein (GRP)-78, a representative ER chaperone, in gastric mucosal cells in primary culture (Tsutsumi et al, 2004). However, it is not known if NSAIDs upregulate other ER chaperones such as ERdj3 and Erdj4, which act as cochaperones for GRP78 and activate the ATPase and refolding activity of GRP78 (Yu et al, 2000;Shen et al, 2002b). Furthermore, it is also not known if NSAIDs induce ER chaperones in other types of cells, such as tumor cells.…”

Section: Introductionmentioning

confidence: 99%

Celecoxib upregulates endoplasmic reticulum chaperones that inhibit celecoxib-induced apoptosis in human gastric cells

et al. 2005

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Nonsteroidal anti-inflammatory drugs (NSAIDs) induce apoptosis in cancer cells and this effect is involved in their antitumor activity. We recently demonstrated that NSAIDs upregulate GRP78, an endoplasmic reticulum (ER) chaperone, in gastric mucosal cells in primary culture. In the present study, induction of ER chaperones by NSAIDs and the effect of those chaperones on NSAID-induced apoptosis were examined in human gastric carcinoma cells. Celecoxib, an NSAID, upregulated ER chaperones (GRP78 and its cochaperones ERdj3 and ERdj4) but also C/EBP homologous transcription factor (CHOP), a transcription factor involved in apoptosis. Celecoxib also upregulated GRP78 in xenograft tumors, accompanying with the suppression of tumor growth in nude mice. Celecoxib caused phosphorylation of eukaryotic translation initiation factor 2 kinase (PERK) and eukaryotic initiation factor-2a (eIF2a) and production of activating transcription factor (ATF)4 mRNA. Suppression of ATF4 expression by small interfering RNA (siRNA) partially inhibited the celecoxib-dependent upregulation of GRP78. Celecoxib increased the intracellular Ca 2 þ concentration, while 1,2-bis(2-aminophenoxy) ethane-N,N,N 0 N 0 -tetraacetic acid, an intracellular Ca 2 þ chelator, inhibited the upregulation of GRP78 and ATF4. These results suggest that the Ca 2 þ -dependent activation of the PERK-eIF2a-ATF4 pathway is involved in the upregulation of ER chaperones by celecoxib. Overexpression of GRP78 partially suppressed the apoptosis and induction of CHOP in the presence of celecoxib and this suppression was stimulated by coexpression of either ERdj3 or ERdj4. On the other hand, suppression of GRP78 expression by siRNA drastically stimulated cellular apoptosis and production of CHOP in the presence of celecoxib. These results show that upregulation of ER chaperones by celecoxib protects cancer cells from celecoxib-induced apoptosis, thus may decrease the potential antitumor activity of celecoxib.

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“…A total of four mammalian ER DnaJ homologues have been identified (21)(22)(23)(24)(25), and it has been proposed that they be referred to as ERdj1-4. In vitro biochemical studies show that the J domains of ERdj1, ERdj3, and ERdj4 can stimulate the ATPase activity of BiP (24 -26), and both ERdj3 and 4 can bind to BiP in vivo (25).…”

mentioning

confidence: 99%

BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP

Chung

Shen

Hendershot

2002

Journal of Biological Chemistry

170

123

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We identified a mammalian BiP-associated protein, BAP, using a yeast two-hybrid screen that shared low homology with yeast Sls1p/Sil1p and mammalian HspBP1, both of which regulate the ATPase activity of their Hsp70 partner. BAP encoded an ϳ54-kDa protein with an N-terminal endoplasmic reticulum (ER) targeting sequence, two sites of N-linked glycosylation, and a C-terminal ER retention sequence. Immunofluorescence staining demonstrated that BAP co-localized with GRP94 in the endoplasmic reticulum. BAP was ubiquitously expressed but showed the highest levels of expression in secretory organ tissues, a pattern similar to that observed with BiP. BAP binding was affected by the conformation of the ATPase domain of BiP based on in vivo binding studies with BiP mutants. BAP stimulated the ATPase activity of BiP when added alone or together with the ER DnaJ protein, ERdj4, by promoting the release of ADP from BiP. Together, these data demonstrate that BAP serves as a nucleotide exchange factor for BiP and provide insights into the mechanisms that control protein folding in the mammalian ER.

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HEDJ, an Hsp40 Co-chaperone Localized to the Endoplasmic Reticulum of Human Cells

Cited by 101 publications

References 35 publications

Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Protogenin Defines a Transition Stage during Embryonic Neurogenesis and Prevents Precocious Neuronal Differentiation

Celecoxib upregulates endoplasmic reticulum chaperones that inhibit celecoxib-induced apoptosis in human gastric cells

BAP, a Mammalian BiP-associated Protein, Is a Nucleotide Exchange Factor That Regulates the ATPase Activity of BiP

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