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Publication : CHOP-Dependent stress-inducible expression of a novel form of carbonic anhydrase VI.

First Author  Sok J Year  1999
Journal  Mol Cell Biol Volume  19
Issue  1 Pages  495-504
PubMed ID  9858573 Mgi Jnum  J:52975
Mgi Id  MGI:1330751 Doi  10.1128/mcb.19.1.495
Citation  Sok J, et al. (1999) CHOP-Dependent stress-inducible expression of a novel form of carbonic anhydrase VI. Mol Cell Biol 19(1):495-504
abstractText  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/EBPbeta 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/ebpbeta-/- cells by exogenous C/EBPbeta 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.
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