title: Oligomerization is not essential for growth suppression by p53 in p53-deficient osteosarcoma Saos-2 cells.
abstract: The carboxy-terminal portion of the p53 protein contains the tetramerization domain, and the introduction of multiple missense mutations in this domain disrupts the formation of p53 tetramers, resulting in the production of dimeric or monomeric forms of p53. It has recently been shown that a single missense or nonsense mutation in this domain affects the functional properties of p53 both in yeast and in mammalian cells. In this study, we tested the oligomerization of p53 with mutations in the oligomerization domain, when expressed in a human osteosarcoma cell line, Saos-2, in vivo. We found that single point mutations, including two missense and two nonsense mutations, in the alpha-helix of the oligomerization domain disrupted the oligomerization of p53, but that p53 still retained its ability to inhibit colony formation of cells to some degree. These results suggest that oligomerization and the carboxy-terminal basic domain are not prerequisite for p53-dependent tumor suppression, and this may explain why few of the tumor-derived p53 mutations that have been examined so far are carboxy-terminal mutations.
authors.affiliation: Department of Clinical Oncology, Tohoku University, Sendai, Japan. chikashi@idac.tohoku.ac.jp
authors.forename: C
authors.initials: C
authors.lastname: Ishioka
authors.forename: H
authors.initials: H
authors.lastname: Shimodaira
authors.forename: C
authors.initials: C
authors.lastname: Englert
authors.forename: A
authors.initials: A
authors.lastname: Shimada
authors.forename: M
authors.initials: M
authors.lastname: Osada
authors.forename: L Q
authors.initials: LQ
authors.lastname: Jia
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: M
authors.initials: M
authors.lastname: Gamo
authors.forename: R
authors.initials: R
authors.lastname: Kanamaru
mesh_terms: D001704:Biopolymers; D002455:Cell Division; D006801:Humans; D009154:Mutation; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D016159:Tumor Suppressor Protein p53