Division of Tumor Virology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Mol Cell Biol 14: 3041-52 (1994)
Abstract
The Epstein-Barr virus BRLF1 and BZLF1 genes are the first viral genes
transcribed upon induction of the viral lytic cycle. The protein
products of both genes (referred to here as Rta and Zta, respectively)
activate expression of other viral genes, thereby initiating the lytic
cascade. Among the viral antigens expressed upon induction of the lytic
cycle, however, Zta is unique in its ability to disrupt viral latency;
expression of the BZLF1 gene is both necessary and sufficient for
triggering the viral lytic cascade. We have previously shown that Zta
can activate its own promoter (Zp), through binding to two Zta
recognition sequences (ZIIIA and ZIIIB). Here we describe mutant Zta
proteins that do not bind DNA (referred to as Zta DNA-binding mutants
[Zdbm]) but retain the ability to transactivate Zp. Consistent with the
inability of these mutants to bind DNA, transactivation of Zp by Zdbm is
not dependent on the Zta recognition sequences. Instead,
transactivation by Zdbm is dependent upon promoter elements that bind
cellular factors. An examination of other viral and cellular promoters
identified promoters that are weakly responsive or unresponsive to Zdbm.
An analysis of a panel of artificial promoters containing one copy of
various promoter elements demonstrated a specificity for Zdbm activation
that is distinct from that of Zta. These results suggest that
non-DNA-binding forms of some transactivators retain the ability to
transactivate specific target promoters without direct binding to DNA.
Mesh Headings
Unique Identifier: 94217702
Gene Symbols
Chemical Identifiers (Names)