DSCP1, a novel TP53-inducible gene, is upregulated by strong genotoxic stresses and its overexpression inhibits tumor cell growth in vitro.
TP53-inducible genes play crucial roles from many biological aspects including cell cycle control, DNA repair, and apoptosis. Herein we report the identification and characterization of a novel TP53-inducible gene, DSCP1 (damage stimulated cytoplasmic protein 1), localized at 17q11. The gene was expressed ubiquitously in normal adult tissues; its protein product was localized mainly in the cytoplasm with anchoring on unknown subcellular structures. Exogenous expression of TP53 induced expression of DSCP1, but more interestingly, DSCP1 was induced by strong genotoxic stresses not only in TP53-maintaining cells but also in TP53-dysfunctioning cells, although the induction was much more efficient in the former than in the latter. In cultured cancer cells, the basal expression level appeared to depend on the functional status of TP53. Moreover, exogenous overexpression of DSCP1 retarded cancer cell growth in vitro. These results indicate that DSCP1 is a stress-inducible gene in both a TP53 dependent and independent manner and that its protein product can inhibit cancer cell growth.
Hata
Tatsuo
T
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Miyagi, Japan.
Ogawa
Takenori
T
Yokoyama
Tada-aki
TA
Fukushige
Shinichi
S
Horii
Akira
A
Furukawa
Toru
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D019556:COS Cells; D002455:Cell Division; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D005822:Genetic Vectors; D006801:Humans; D015151:Immunoblotting; D017404:In Situ Hybridization, Fluorescence; D066298:In Vitro Techniques; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009153:Mutagens; D009154:Mutation; D009369:Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation
D009153:Mutagens; D012333:RNA, Messenger; C492526:TP53I13 protein, human; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins