Identification of novel stress-induced genes downstream of chop

Xiao Zhong Wang, Masahiko Kuroda, John Sok, Nikoleta Batchvarova, Robin Kimmel, Peter Chung, Helene Zinszner, David Ron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

258 Scopus citations

Abstract

CHOP (GADD153) is a small nuclear protein that dimerizes avidly with members of the C/EBP family of transcription factors. Normally undetectable, it is expressed at high levels in cells exposed to conditions that perturb protein folding in the endoplasmic reticulum and induce an endoplasmic reticulum stress response. CHOP expression in stressed cells is linked to the development of programmed cell death and, in some instances, cellular regeneration. In this study, representational difference analysis was used to compare the complement of genes expressed in stressed wild-type mouse embryonic fibroblasts with those expressed in cells nullizygous for chop. CHOP expression, in concert with a second signal, was found to be absolutely required for the activation by stress of a set of previously undescribed genes referred to as DOCs (for downstream of CHOP). DOC4 is a mammalian ortholog of a Drosophila gene, Tenm/Odz, implicated in patterning of the early fly embryo, whereas DOC6 encodes a newly recognized homolog of the actin-binding proteins villin and gelsolin. These results reveal the existence of a novel CHOP-dependent signaling pathway, distinct from the known endoplasmic reticulum unfolded protein response, which may mediate changes in cell phenotype in response to stress.

Original languageEnglish (US)
Pages (from-to)3619-3630
Number of pages12
JournalEMBO Journal
Volume17
Issue number13
DOIs
StatePublished - Jul 1 1998

Keywords

  • Endoplasmic reticulum
  • Gene targeting
  • Subtractive hybridization

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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