title: Regulation of apoptosis by p53-inducible transmembrane protein containing sushi domain.
abstract: The tumor suppressor p53 is a transcription factor that induces the transcription of various target genes in response to DNA damage and it protects the cells from malignant transformation. In this study, we performed cDNA microarray analysis and found that the transmembrane protein containing sushi domain (TMPS) gene, which encodes a putative type I transmembrane protein, is a novel p53-target gene. TMPS contains a sushi domain in the extracellular region, which is associated with protein-protein interaction. TMPS expression is induced by endogenous p53 under genotoxic stress in several cancer cell lines. Reporter assay revealed p53-dependent transactivation of the p53 binding-sites (BSs) located in the intron 1 of TMPS. Chromatin immunoprecipitation (ChIP) assay showed that p53 binds to these BSs in vivo. Overexpression of TMPS induced apoptosis through the activation of caspase-3, 8, and 9 in various cancer cell lines. Moreover, γ-irradiation induced the expression of TMPS mRNA in the spleen and colon of p53+/+ mice but not in those of p53-/- mice. These data indicate that TMPS may play a role in p53-dependent apoptosis under DNA damage condition.
authors.affiliation: Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Cui
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kamino
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Kitamura
authors.forename: Takafumi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Daisuke
authors.initials: D
authors.lastname: Shinogi
authors.forename: Olga
authors.initials: O
authors.lastname: Goda
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Arakara
authors.forename: Manabu
authors.initials: M
authors.lastname: Futamura
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D045744:Cell Line, Tumor; D045325:HCT116 Cells; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D040081:Protein Array Analysis; D017434:Protein Structure, Tertiary; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53