RGD Reference Report - Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. - Rat Genome Database

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Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state.

Authors: McCullough, KD  Martindale, JL  Klotz, LO  Aw, TY  Holbrook, NJ 
Citation: McCullough KD, etal., Mol Cell Biol 2001 Feb;21(4):1249-59.
RGD ID: 70575
Pubmed: PMID:11158311   (View Abstract at PubMed)
PMCID: PMC99578   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.21.4.1249-1259.2001   (Journal Full-text)

gadd153, also known as chop, is a highly stress-inducible gene that is robustly expressed following disruption of homeostasis in the endoplasmic reticulum (ER) (so-called ER stress). Although all reported types of ER stress induce expression of Gadd153, its role in the stress response has remained largely undefined. Several studies have correlated Gadd153 expression with cell death, but a mechanistic link between Gadd153 and apoptosis has never been demonstrated. To address this issue we employed a cell model system in which Gadd153 is constitutively overexpressed, as well as two cell lines in which Gadd153 expression is conditional. In all cell lines, overexpression of Gadd153 sensitized cells to ER stress. Investigation of the mechanisms contributing to this effect revealed that elevated Gadd153 expression results in the down-regulation of Bcl2 expression, depletion of cellular glutathione, and exaggerated production of reactive oxygen species. Restoration of Bcl2 expression in Gadd153-overexpressing cells led to replenishment of glutathione and a reduction in levels of reactive oxygen species, and it protected cells from ER stress-induced cell death. We conclude that Gadd153 sensitizes cells to ER stress through mechanisms that involve down-regulation of Bcl2 and enhanced oxidant injury.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ER overload response  IMP 70575 RGD 
regulation of DNA-templated transcription  IDA 70575 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ddit3  (DNA-damage inducible transcript 3)


Additional Information