title: Dominant-negative mutants are clustered in a domain of the human T-cell leukemia virus type I Rex protein: implications for trans dominance.
abstract: The 27-kDa Rex trans-acting protein appears to be essential for replication of human T-cell leukemia virus type I. Mutations introduced outside of the Rex RNA-binding domain-nucleolar localization signal display either wild-type activity or, conversely, yield dominant-negative proteins. We generated missense mutations in a particular domain of the Rex protein (amino acid residues 54 to 69) which is characterized by a cluster of dominant-negative mutants. Our results indicate that amino acids 57 to 67 are critically important for Rex function mediated through the RxRE cis-acting RNA sequence. Within this domain, only amino acids 61 to 63 could be mutated without loss of function. All other missense and deletion mutants yielded dominant-negative proteins. In vitro RNA-binding studies performed with glutathione S-transferase-Rex fusion proteins demonstrated that all of the mutant Rex proteins interacted specifically with RxRE RNA. Analysis of chimeric Rex-Rev proteins suggests that this Rex domain is important for oligomerization.
authors.affiliation: SANDOZ Research Institute, Vienna, Austria.
authors.forename: I
authors.initials: I
authors.lastname: Weichselbraun
authors.forename: J
authors.initials: J
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Dobrovnik
authors.forename: H
authors.initials: H
authors.lastname: Bogerd
authors.forename: R
authors.initials: R
authors.lastname: Grassmann
authors.forename: W C
authors.initials: WC
authors.lastname: Greene
authors.forename: J
authors.initials: J
authors.lastname: Hauber
authors.forename: E
authors.initials: E
authors.lastname: Böhnlein
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004279:DNA, Viral; D016370:Gene Products, rex / Q000235:genetics*; D005799:Genes, Dominant; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016415:Sequence Alignment
chemical_list: D004279:DNA, Viral; D016370:Gene Products, rex