title: A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization.
abstract: The p53 gene product has been implicated in both human and animal tumorigenesis. p53 forms heterologous complexes with the transforming proteins encoded by several different DNA tumor viruses. p53 also assembles into stable homo-oligomers. We demonstrate that the major structural determinant for the tetramerization of p53 is an alpha-helical plus basic region motif near the C-terminus of the protein. A monomeric p53 mutant adopts a conformation distinct from both 'wild-type' and 'mutant' form as defined by PAb1620 and PAb240 monoclonal antibody recognition. Nevertheless, monomeric and dimeric mutant p53 proteins retain the ability to suppress SV40 origin-directed DNA replication in vivo. Thus, p53-p53 interaction and expression of the PAb1620 epitope is not a prerequisite for such activity. We present data suggesting that suppression of replication by p53 may occur by a mechanism that is independent of detectable p53-T antigen association.
authors.affiliation: Cell Proliferation Laboratory, Marie Curie Research Institute, Surrey, UK.
authors.forename: H W
authors.initials: HW
authors.lastname: Stürzbecher
authors.forename: R
authors.initials: R
authors.lastname: Brain
authors.forename: C
authors.initials: C
authors.lastname: Addison
authors.forename: K
authors.initials: K
authors.lastname: Rudge
authors.forename: M
authors.initials: M
authors.lastname: Remm
authors.forename: M
authors.initials: M
authors.lastname: Grimaldi
authors.forename: E
authors.initials: E
authors.lastname: Keenan
authors.forename: J R
authors.initials: JR
authors.lastname: Jenkins
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D004261:DNA Replication / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D008969:Molecular Sequence Data; D010957:Plasmids / Q000235:genetics; D011487:Protein Conformation; D013539:Simian virus 40 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53