CHOP-dependent stress-inducible expression of a novel form of carbonic anhydrase VI

John Sok, Xiao Zhong Wang, Nikoleta Batchvarova, Masahiko Kuroda, Heather Harding, David Ron*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

117 Scopus citations

Abstract

CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducible CA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VI expression in c/ebpβ(-/-) cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

Original languageEnglish (US)
Pages (from-to)495-504
Number of pages10
JournalMolecular and cellular biology
Volume19
Issue number1
DOIs
StatePublished - Jan 1999

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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