title: Transcriptional specificity in various p53-mutant cells.
abstract: Mutation of the tumor suppressor gene p53 is the most common genetic alteration observed in human tumors. However, the relationship between the mutation point of p53 and the transcriptional specificity is not so obvious. We prepared Saos-2 cells with various mutations of p53 that are found in human tumors, and examined the resulting transcriptional alterations in the cells. Loss of function and gain of function were observed in all p53 mutants. Hot-spot mutations of p53 are frequently found in tumor cells. We compared hot-spot mutations and other mutations of p53 and found that a more than 2-fold transcription of CADPS2, PIWIL4 and TRIM9 was induced by hot spot mutations, but not by other mutations. As PIWIL4 suppresses the p16(INK4A) and ARF pathway, restraining cell growth and genomic instability, induction of PIWIL4 expression may be one reason why hot-spot mutations are frequently found in tumor cells.
authors.affiliation: Department of Radioisotope Medicine, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, 12-4 Sakamoto 1-chome, Nagasaki 852, Japan. okaichi@nagasaki-u.ac.jp
authors.forename: Kumio
authors.initials: K
authors.lastname: Okaichi
authors.forename: Nanaka
authors.initials: N
authors.lastname: Izumi
authors.forename: Yuma
authors.initials: Y
authors.lastname: Takamura
authors.forename: Shoichi
authors.initials: S
authors.lastname: Fukui
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
mesh_terms: D060565:Argonaute Proteins / Q000502:physiology; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D016601:RNA-Binding Proteins; D014158:Transcription, Genetic; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D060565:Argonaute Proteins; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C556795:PIWIL4 protein, human; D016601:RNA-Binding Proteins; D000070584:Tripartite Motif Proteins; C550446:TRIM9 protein, human; D044767:Ubiquitin-Protein Ligases