The Epstein-Barr virus Zta transactivator: a member of the bZIP family with unique DNA-binding specificity and a dimerization domain that lacks the characteristic heptad leucine zipper motif.

AUTOR(ES)

Chang, Y N

RESUMO

Introduction of the zta gene of Epstein-Barr virus into latently infected B cells leads to induction of the entire lytic cycle program of the virus. The Zta gene product is a sequence-specific DNA-binding protein of 35 kilodaltons that behaves as a specific transcriptional transactivator in transient cotransfection assays. All known Zta-responsive target promoters contain one or more members of a family of consensus-binding sites known as ZREs. On the basis of the presence of limited amino acid similarity within a basic carboxy-terminal domain, Zta has been proposed to be a highly divergent member of the c-Jun/c-Fos/GCN4 family of AP-1-binding proteins. We show here that in vitro-translated Zta and the Jun:Fos proteins have overlapping but distinct target DNA-binding specificies; both recognize canonical AP-1 sites, but only Zta recognizes ZRE sites and only Jun:Fos recognizes CRE sites. The relative binding affinity of Zta for oligonucleotides containing the 7-base-pair c-Fos AP-1 site TGAGTCA was twofold greater than that for the ZRE core motifs TGAGCAA, TG TGCAA, and TGAGTAA, but 10-fold greater than that for TGTGTCA, as measured by gel mobility retardation and competition DNA-binding assays. Cross-linking and cotranslational heterodimerization assays showed that like GCN4, Zta forms a stable homodimer in both its DNA-bound and unbound forms. Furthermore, we show that a potential coiled-coil helical domain adjacent to the basic domain of Zta can substitute for the leucine zipper of c-Fos to produce a DNA-binding protein that has a very stringent target DNA specificity and can only recognize symmetric 9-base-pair AP-1 sites (ATGAGTCAT). Therefore, despite the absence of the repeated heptad leucine zipper motifs, the Zta protein retains the characteristic features of a juxtaposed basic region and an exactly aligned coiled-coil alpha-helical dimerization domain of the bZIP class of transcriptional regulatory factors.

Documentos Relacionados

• In vitro transcriptional activation, dimerization, and DNA-binding specificity of the Epstein-Barr virus Zta protein.
• The Zipper Region of Epstein-Barr Virus bZIP Transcription Factor Zta Is Necessary but Not Sufficient To Direct DNA Binding
• Evidence for coiled-coil dimer formation by an Epstein-Barr virus transactivator that lacks a heptad repeat of leucine residues.
• The DNA-binding domain of two bZIP transcription factors, the Epstein-Barr virus switch gene product EB1 and Jun, is a bipartite nuclear targeting sequence.
• A replication function associated with the activation domain of the Epstein-Barr virus Zta transactivator.