TRANSACTIVATION OF A CELLULAR PROMOTER BY THE NS1 PROTEIN OF PARVOVIRUS MINUTE VIRUS OF MICE THROUGH A PUTATIVE HORMONE-RESPONSIVE ELEMENT

The promoter of the thyroid hormone receptor cr gene (c-ErbA-1) is act ivated by the nonstructural protein 1 (NS1) of parvovirus minute virus of mice (prototype strain [MVMp]) in ras-transformed FREJ4 cells that are permissive for lytic MVMp replication. This stimulation may be re lated to the sensitivity of host cells to MVMp, as it does not take pl ace in parental FR3T3 cells, which are resistant to the parvovirus kil ling effect. The analysis of a series of deletion and point mutants of the c-erbA-1 promoter led to the identification of an upstream region that is necessary for NS1-driven transactivation. This sequence harbo rs a putative hormone-responsive element and is sufficient to render a minimal promoter NS1 inducible in FREJ4 but not in FR3T3 cells, and i t is involved in distinct interactions with proteins from the respecti ve cell lines. The NS1-responsive element of the c-erbA-1 promoter bea rs no homology with sequences that were previously reported to be nece ssary for NS1 DNA binding and transactivation. Altogether, our data po int to a novel, cell-specific mechanism of promoter activation by NS1.