Transactivation of the grp78 promoter by malfolded proteins, glycosylation block, and calcium ionophore is mediated through a proximal region containing a CCAAT motif which interacts with CTF/NF-I.

or other conformational changes. Inthis study, we provide evidence atthetranscriptional level that aconformationally abnormal protein, an altered herpes simplex virus type1envelope protein thatisretained intheER ofa mammalian cellline, transactivates thegrp78 promoter. Incontrast, thenormalviral envelope glycoprotein doesnotelevate grp78 promoter activity. Using a series of5'deletions, linker-scanning, andinternal deletion mutations spanning a 100-bp region from-179to-80,we correlate thecis-acting regulatory elements mediating theactivation ofgrp78bymalfolded proteins, glycosylation block, andthecalcium ionophore A23187. We showthattheyallactthrough thesame control elements, suggesting thattheyshare a common signal. We report herethat thehighly conserved grpelement, while important forbasal level andinduced grp78 expression, isfunctionally redundant. Thesingle mostimportant element, bylinker-scanning analysis, isa 10-bp region thatcontains a CCAATmotif. Italone isnotsufficient forpromoteractivity, buta40-bpregion (-129to-90)thatcontains this motif isessential formediating basal level andstress inducibility ofthegrp78 promoter. We showthat thetranscription factor CTF/NF-I isable totransactivate thegrp78 promoter through interaction withthis CCAATmotif. Ithasbeenproposed thatcellular proteins ofa class generally referred toaschaperones havetheability tobind toproteins fortransmembrane targeting andmay also participate intheassembly ofoligomeric proteins (56). Included among theATP-dependent chaperones isthe78-kDaglucose-regulated protein GRP78,whichisaresident protein in theendoplasmic reticulum (ER).Although GRP78was first