Induction of the mammalian GRP78/BiP gene by Ca2+ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1.

Previously, we have identified a constitutive nuclear factor, p70CORE, from HeLa cell nuclear extract which interactsspecificallywiththestress-induciblechangeregion(SICR)ofthegrp78promoter.Herewereportthat p70CORE is identical to YY1, a member of the GLI zinc finger family, by criteria of biochemical properties including apparent molecular weight, binding site homology, immunoreactivity, and affinity purification. Recombinant YY1 binds the double-stranded SICR with high specificity but has no affinity for its singlestranded form. In cotransfection studies, YY1 specifically enhanced the transcriptional activation of thegrp78 promoter under a variety of stress conditions: depletion of the endoplasmic reticulum calcium stores, protein glycosylation block, and formation of aberrant proteins by azetidine treatment. In contrast, YY1 has minimal effectonthestressinductionofthehsp70promoter.YY1enhancementofthegrp78stressresponseisdependent on its DNA-binding domain, with little effect on the basal expression of the promoter. The effect of YY1 transactivation may be mediated by the highly conservedgrp78core element. This is thefirst example of the ubiquitousfactorYY1involvedinregulatinginduciblegeneexpressionanditsinvolvementinmediatingstress signals generated from the endoplasmic reticulum to the nucleus.