MUTATIONAL ANALYSIS OF HUMAN FOAMY VIRUS BEL1 ACTIVATION DOMAIN

Abstract

The Bell transactivator of human foamy virus is a 300-amino acid nuclear protein with a strong distinct autonomous activation domain (AD) from residues 263 to 292 and an HFV LTR-directed augmenting domain from residues 255 to 266, To delineate the mechanistic action of AD, we generated several missense mutations and tested for their transactivation abilities, Our results showed that the aromaticity or specific indole ring structure of Trp-279 and the hydrophobic character of Phe-278 critical for the activity of Bell AD. We also demonstrated that other acidic and proline residues appear to be dispensable for transactivation. In addition, mutational analysis of the intact Bell showed that Leu-259 and Leu-260 residues are important for the transactivation function of the HFV LTR-directed augmenting domain. An in vivo competition analysis indicated that the overexpression of wild type Bell and Bel1(1-260)/p53(1-73) chimeric protein strongly inhibited the transactivation ability of both Ga14-Bel1(263-292) and Gal4-p53(1-42). These results suggested that a common cellular target may be shared by ADs of both Bell and p53.