Identification of novel stress-induced genes downstream of chop

Wang, Xiao Zhong; Kuroda, Masahiko; Sok, John C.; Batchvarova, Nikoleta; Kimmel, Robin A.; Chung, Peter; Zinszner, Hélène; Ron, David

doi:10.1093/emboj/17.13.3619

Cited by 292 publications

(260 citation statements)

References 49 publications

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“…58 Using representative difference analysis, Ron and colleagues found three target genes of CHOP that they referred to as DOCs (for downstream of CHOP). 60,61 DOC1 is a stress-inducible form of carbonic anhydrase VI, which is predicted to increase the proton concentration and to decrease intracellular pH. DOC4 is a homologue of Tenm/Odz, which might function in signaling at compartment boundaries.…”

Section: Downstream Of Chop In Er Stress-induced Apoptosismentioning

confidence: 99%

Roles of CHOP/GADD153 in endoplasmic reticulum stress

2003

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Endoplasmic reticulum (ER) is the site of synthesis and folding of secretory proteins. Perturbations of ER homeostasis affect protein folding and cause ER stress. ER can sense the stress and respond to it through translational attenuation, upregulation of the genes for ER chaperones and related proteins, and degradation of unfolded proteins by a quality-control system. However, when the ER function is severely impaired, the organelle elicits apoptotic signals. ER stress has been implicated in a variety of common diseases such as diabetes, ischemia and neurodegenerative disorders. One of the components of the ER stress-mediated apoptosis pathway is C/EBP homologous protein (CHOP), also known as growth arrestand DNA damage-inducible gene 153 (GADD153). Here, we summarize the current understanding of the roles of CHOP/ GADD153 in ER stress-mediated apoptosis and in diseases including diabetes, brain ischemia and neurodegenerative disease.

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Section: Downstream Of Chop In Er Stress-induced Apoptosismentioning

confidence: 99%

Roles of CHOP/GADD153 in endoplasmic reticulum stress

2003

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“…Similarly to ATF6, the IRE1 fragments enter the nucleus and upregulate ER stressresponsive genes. 65 The IRE-mediated response is, however, slower than that mediated by ATF6, because it occurs via processing the mRNA for XBP1, which is induced by active ATF6. Splicing of a small intron from the XBP1 mRNA is carried out by the ribonuclease activity of IRE1 and generates an active transcription factor.…”

Section: Gangliosides and The Er Stress Responsementioning

confidence: 99%

Gangliosides as apoptotic signals in ER stress response

d’Azzo

Tessitore²,

Sano

2006

Cell Death Differ

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Renewed attention has been given lately to gangliosides and to their function as intracellular messengers of the adaptive responses to stress. Gangliosides are vital components of cell membranes; therefore, deleterious consequences can result from changes in their chemical composition and concentration, that is, membrane dynamics and structure can be altered as can the behavior of other membrane proteins. The importance of gangliosides in human health is evident in neurodegenerative diseases associated with defects in their degradation. As key modulators of intracellular calcium flux, gangliosides are involved in cellular processes downstream of calcium signaling. In this review, we focus on the effect of ganglioside accumulation on the endoplasmic reticulum calcium homeostasis and on the integrity of the mitochondrial membranes. We discuss how these events elicit an apoptotic program that ultimately leads to cell death. Owing to interorganelle crosstalk, these events are not necessarily self-contained, and gangliosides may serve as the common factor.

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“…18 Because CHOP functions as a transcription factor, there must be a target gene(s), the transcription of which is activated by CHOP, and whose product(s) functions in the apoptosis signal cascade. Wang et al 19 found candidate target genes of the CHOP protein when using representational difference analysis. However, these genes are distinct from known factors involved in the ER stress response and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria

et al. 2004

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We reported that the endoplasmic reticulum (ER) stress pathway involving CHOP, a member of the C/EBP transcription factor family, plays a key role in nitric oxide (NO)-mediated apoptosis of macrophages and pancreatic b cells. We also showed that the cytosolic chaperone pair of hsp70 and dj1 (hsp40/hdj-1) or dj2 (HSDJ/hdj-2) prevents NO-mediated apoptosis upstream of cytochrome c release from mitochondria. To analyze roles of the chaperone pair in preventing apoptosis, RAW 264.7 macrophages stably expressing hsp70 and dj1 or dj2 were established. The chaperone pair prevented LPS/IFN-c-induced and NO-mediated apoptosis downstream of CHOP induction. hsp70 mutant protein lacking the ATPase domain or the C-terminal EEVD sequence were not effective in preventing CHOP-induced apoptosis. A mutant dj2 lacking the C-terminal prenylation CaaX motif, was also not effective. When wild-type RAW 264.7 cells were treated with LPS/IFN-c, NOmediated apoptosis was induced, and proapoptotic Bcl-2 family protein Bax was translocated from cytosol to mitochondria. This translocation was prevented in cells stably expressing hsp70/dj2, and in CHOP knockout cells. Overexpression of CHOP in wild-type cells also induced translocation of Bax and this translocation was prevented in cells expressing hsp70/dj2. CHOP-induced apoptosis was prevented by Bax knock-down. Coimmunoprecipitation experiments showed that Bax interacts with both hsp70 and dj1/dj2. ATPase domain of hsp70 was necessary for the binding with Bax. These findings indicate that CHOP-induced apoptosis is mediated by translocation of Bax from the cytosol to the mitochondria, and hsp70/dj1 or dj2 chaperone pair prevents apoptosis by interacting with Bax and preventing translocation to the mitochondria.

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Identification of novel stress-induced genes downstream of chop

Cited by 292 publications

References 49 publications

Roles of CHOP/GADD153 in endoplasmic reticulum stress

Roles of CHOP/GADD153 in endoplasmic reticulum stress

Gangliosides as apoptotic signals in ER stress response

hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondria

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