Isolation of a novel TP53 target gene from a colon cancer cell line carrying a highly regulated wild-type TP53 expression system.
We established a colon cancer cell line SW480-LOWTP53-1 carrying a wild-type TP53 transgene that is inducible under control of the lactose operon. Induction of this transgene by isopropyl-beta-D-thiogalactoside (IPTG) arrests growth of the transfected cells. To investigate cellular responses related to the TP53 signaling pathway to induce growth arrest, we applied a differential display method to screen mRNAs isolated from this cell line and looked for genes whose expression was activated or suppressed after induction of wild-type TP53. Subsequent Northern blot analysis confirmed that expression of one novel gene was regulated by wild-type TP53. The cDNA, termed TP53TG1 (TP53 target gene 1), contained an open reading frame of 270 nucleotides encoding 90 amino acids. Under conditions of cellular stress (ultraviolet irradiation or exposure to bleomycin or cisplatin), expression of TP53TG1 was induced in a wild-type TP53-dependent manner, indicating that this gene is likely to play an important role in the signaling pathway of TP53 and may function in response to cellular damage.
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan.
Y
Y
Takei
S
S
Ishikawa
T
T
Tokino
T
T
Muto
Y
Y
Nakamura
D000595:Amino Acid Sequence; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005796:Genes / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D016158:Genes, p53 / Q000187:drug effects / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D007544:Isopropyl Thiogalactoside / Q000494:pharmacology; D008969:Molecular Sequence Data; D019076:Transgenes / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects / Q000235:genetics*
D004268:DNA-Binding Proteins; C114495:TP53TG1 protein, human; D016159:Tumor Suppressor Protein p53; D007544:Isopropyl Thiogalactoside