N-terminal transcriptional activation domain of LZIP comprises two LxxLL motifs and the Host Cell Factor-1 binding motif

Host Cell Factor-1 (HCF-1. C1)was first identified as a cellular target for the herpes simplex virus transcriptional activator VP16. Association betwe en HCF and VP16 leads to the assembly of a multiprotein enhancer complex th at stimulates viral immediate-early gene transcription. HCF-1 is expressed in all cells and is required for progression through G(1) phase of the cell cycle. In addition to VP16. HCF-1 associates with a cellular bZIP protein known as LZIP (or Luman). Both LZIP and VP16 contain a four-amino acid HCF- binding motif, recognized by the N-terminal beta-propeller domain of HCF-1. Herein, we show that the N-terminal 92 amino acids of LZIP contain a poten t transcriptional activation domain composed of three elements: the HCF-bin ding motif and two LxxLL motifs. LxxLL motifs are found in a number of tran scriptional coactivators and mediate protein-protein interactions, notably recognition of the nuclear hormone receptors. LZIP is an example of a seque nce-specific DNA-binding protein that uses LxxLL motifs within its activati on domain to stimulate transcription. The LxxLL motifs are not required for association with the HCF-1 beta-propeller and instead interact with other regions in HCF-1 or recruit additional cofactors.