A NEW MEMBER OF THE LEUCINE ZIPPER CLASS OF PROTEINS THAT BINDS TO THE HLA DR-ALPHA PROMOTER

Several mutants derived from transformed human B cell lines are defective in expressing major histocompatibility complex (MHC) dass II genes. The failure to express a class II gene in at least one such mutant line has been mapped to the MHC class II X box, a conserved transcriptional element in the promoter region. A complementary DNA encoding a DNA-binding protein (human X box binding protein, hXBP-1) whose target is the human DRα X box and the 3′ flanking region has now been cloned. This complementary DNA encoded a protein with structural similarities to the c-jun proto-oncogene product, and its target sequence was closely related to the palindromic target sequence of c-jun. Mutation of the hXBP-1 DNA target sequence decreased DRα promoter activity in vivo. These studies suggest that the hXBP-1 protein acts as a transcription factor in B cells.