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.

journal_name

Oncol Rep

journal_title

Oncology reports

authors

Cui H,Kamino H,Nakamura Y,Kitamura N,Miyamoto T,Shinogi D,Goda O,Arakara H,Futamura M

doi

10.3892/or_00000972

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

1193-200

issue

5

eissn

1021-335X

issn

1791-2431

journal_volume

24

pub_type

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