Expression of zinc-finger protein 143 (ZNF143), a human homolog of the Xenopus transcriptional activator protein Staf, is induced by various DNA-damaging agents including etoposide, doxorubicin, and γ-irradiation. ZNF143 binds to cisplatin-modified DNA, and its levels are increased in cancer cells that are resistant to anticancer drugs, including cisplatin, suggesting that it plays a role in carcinogenesis and cancer cell survival. However, the mechanism of ZNF143 induction in cancer cells remains unclear. Both insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) have been reported to be overexpressed in cancer cells and to be related to anticancer drug resistance, but the identity of the relevant signaling mediators is still being investigated. In the present study, we observed that IGF-1 was able to induce ZNF143 expression in HCT116 human colon cancer cells and that wortmannin, an inhibitor of phosphatidylinositide 3-kinase (PI3-kinase), inhibited this induction, as did diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, and monodansylcardavarine (MDC), a receptor internalization inhibitor. Treatment with MDC decreased the IGF-1-stimulated generation of reactive oxygen species. Taken together, these data suggest that IGF-1 induces ZNF143 expression in cancer cells via PI3-kinase and reactive oxygen species generation during receptor internalization.

Abstract. Though the number of completely sequenced genomes quickly grows in recent years, the methods to predict protein functions by homology from the genomes have not been used sufficiently. It has been a successful technique to construct an OPCs(Orthologous Protein Clusters) with the best reciprocal BLAST hits from multiple complete-genomes. But it takes time-consumingprocesses to make the OPCs with manual work. We, here, propose an automatic method that clusters OPs(Orthologous Proteins) from multiple completegenomes, which is, to be extended, based on INPARANOID which is an automatic program to detect OPs between two complete-genomes. We also prove all possible clustering mathematically.

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