LUMAN, A NEW MEMBER OF THE CREB ATF FAMILY, BINDS TO HERPES-SIMPLEX VIRUS VP16-ASSOCIATED HOST CELLULAR FACTOR/

The human host cell factor (HCF) is expressed in a variety of adult an d fetal tissues, and its gene is conserved in animals as diverse as ma mmals and insects, However, its only known function is to stabilize th e herpes simplex virus virion transactivator VP16 in a complex with th e cellular POU domain protein Oct-1 and cis-acting regulatory elements in promoters of immediate-early viral genes. To identify a cellular f unction for HCF, we used the yeast two-hybrid system to identify a cel lular ligand for HCF. This protein, Luman, appears to be a cyclic AMP response element (CRE)-binding protein/activating transcription factor 1 protein of the basic leucine zipper superfamily. It binds CREs in v itro and activates CRE-containing promoters when transfected into COS7 cells, This activation of transcription was synergistically enhanced by the presence of CCAAT/enhancer-binding protein elements and inhibit ed by AP-1 elements in the promoter. In addition to a basic DNA bindin g domain, Luman possesses an unusually long leucine zipper and an acid ic amino-terminal activation domain, These features in Luman are also present in what appear to be homologs in the mouse, Drosophila melanog aster, and Caenorhabditis elegans, Luman and VP16 appear to have simil ar mechanisms for binding HCF, as in vitro each competitively inhibite d the binding of the other to HCF. In transfected cells, however, whil e VP16 strongly inhibited the ability of GAL-Luman to activate transcr iption from a GAL4 upstream activation sequence-containing promoter, L uman was unable to inhibit the activity of GAL-VP16. Luman appears to be a ubiquitous transcription factor, and its mRNA was detected in all human adult and fetal tissues examined, The possible role of HCF in r egulating the function of this ubiquitous transcription factor is disc ussed.