Binding of RBP-Jκ (CSL) protein to the promoter of the Kaposi's sarcoma-associated herpesvirus ORF47 (gL) gene is a critical but not sufficient determinant of transactivation by ORF50 protein

ORF50 protein activates the KSHV lytic cycle. The promoter of an early lytic-cycle gene ORF47, encoding envelope protein gL, is activated by an interaction between ORF50 protein and RBP-J kappa. In ORF47p only one of two sequences fitting the consensus RBP-J kappa recognition site strongly binds RBP-J kappa and confers a response to ORF50 protein. Flanking sequences 5' to the RBP-J kappa binding site are required to confer a maximal response to ORF50 protein. Not all mutant ORF50 response elements in the ORF47p that are bound by RBP-J kappa are sufficient to confer maximal ORF50 responsiveness. Four sequences containing an RBP-J kappa site and flanking sequences characteristic of the ORF50 response element in ORF47p were identified in human DNA. All bound RBP-J kappa, but only one responded robustly to ORF50 protein. We propose models for the possible function of ancillary sequences flanking the RBP-J kappa-binding element which are crucial for mediating ORF50 transactivation. (C) 2009 Elsevier Inc. All rights reserved.