CONFORMATION-DEFECTIVE HERPES-SIMPLEX VIRUS-1 GLYCOPROTEIN-B ACTIVATES THE PROMOTER OF THE GRP94 GENE THAT CODES FOR THE 94-KD STRESS PROTEIN IN THE ENDOPLASMIC-RETICULUM

GRP94 is a major glycoprotein in the endoplasmic reticulum with calciu m-binding properties. Recently, GRP94 has been shown to bind to unasse mbled forms of multimeric proteins and peptides. We report here that G RP94 forms a stable association with the mutated form of the herpes si mplex type virus 1 (HSV-1) glycoprotein B, but not with the fully proc essed viral protein. Both the glycosylated and unglycosylated forms of GRP94 are capable of complexing with the mutated, conformation-defect ive viral glycoprotein. Cotransfection of expression vectors for gB an d grp94 promoter fusion genes revealed that the grp94 promoter is stro ngly activated by the mutant form of gB. Analysis of the grp94 promote r mutants showed that two regions in the promoter, a highly conserved element referred to as grp core and the CCAAT element most proximal to the TATA element (C1), mediate the induction of grp94 by malfolded pr otein. We further determined that the grp94 core and C1 element bind t o common as well distinct nuclear factors from grp78, a commonly coreg ulated gene. Through UV cross-linking, site competition, and immuno-cr oss-reactivity, we identified that the heteromeric CCAAT-binding prote in (CBF) is one component of the grp94 C1 complex.