| Summary: | 碩士 === 長庚大學 === 基礎醫學研究所 === 93 === NPM/B23 (Nucleophosmin/B23) is a major nucleolar protein and it plays a major role in centrosome replication, which couples to cell-cycle events. Many anticancer drugs cause dissociation of NPM from nucleoli to the nucleoplasm (NPM-translocation). Current projects include studies of the mechanism of drug-induced NPM-translocation and its relationship with apoptosis and DNA repair. NPM/B23 was rapidly up-regulated after UV irradiation(at 254 nm; 30J/m2) in NIH 3T3 cells and HeLa/S3 cells, and it was characteristic of immediate-early gene response and increased expression of PCNA. Many DNA-damaged drugs can also induce many DNA repair-associated gene expression include PCNA(proliferating cell nuclear antigen)and GADD45. Previous study had also been found that nucleophosmin/B23 is rapidly up-regulated after UV irradiation as p53, PCNA or c-Jun and over-expression of NPM/B23 can increase PCNA promoter activity, but the mechanism is unknown.
The transcription factor YY1 associates with the initiator element of the PCNA promoter and mediate the promoter activity of PCNA. It also been found that YY1 could interact with NPM/B23. In this study, we use the late stage MGH-U1 bladder cancer cell as a model to determine the relationship of NPM/B23, PCNA and YY1 and the role of NPM/B23 in regulation of PCNA promoter after treatment with DNA-damaged drug, doxorubicin.
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