title: Artificial regulation of p53 function by modulating its assembly.
abstract: The tumor suppressor p53, a 393-amino acid transcription factor with four domains, induces cell cycle arrest, senescence, and apoptosis in response to diverse stress. Tetramer formation is critical for the function of p53. The tetramerization domain permits the tetramerization of p53, where bundled four DNA-binding domains recognize the specific target DNA sequences and activate hundreds of genes, which lead to the various cell fates. Here we show that tumor suppressive functions of p53 can be regulated by manipulating tetramer formation of an engineered p53, in which tetramerization domain of p53 is replaced with an inducible tetramer forming protein. This result suggests that artificial regulation of p53 activity by the engineered p53 is a useful tool to investigate the tumor suppression mechanism of p53 and to combat cancer.
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, 3190 Gofuku, Toyama-shi, Toyama, 930-8555, Japan. Electronic address: inobe@ctg.u-toyama.ac.jp.
authors.forename: Tomonao
authors.initials: T
authors.lastname: Inobe
authors.affiliation: Frontier Research Core for Life Sciences, University of Toyama, 3190 Gofuku, Toyama-shi, Toyama, 930-8555, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Nozaki
authors.affiliation: Laboratory of Structural Neuropathology, Doshisha University Graduate School of Brain Science, 1-3 Tatara Miyakodani, Kyotanabe-shi, Kyoto, 610-0394, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Nukina
mesh_terms: D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D015202:Protein Engineering; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D011993:Recombinant Fusion Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D022021:Tacrolimus Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins
keywords: Chemically induced oligomerization; FKBP; FRB; Protein engineering; Rapamycin; p53