Potential negative regulation of damage-recognition proteins in cisplatin-resistant HeLa cells in response to DNA damage.
Nuclear proteins in cisplatin-resistant (CPR) and non-resistant HeLa cells were assayed by 2-dimensional polyacrylamide gel electrophoresis. The levels of at least 4 suppressible nuclear proteins were reduced in CPR cells. These proteins were partially restored in CPR revertants that are known to be less capable of repairing cisplatin-DNA adducts. Southwestern blotting assays indicate that in CPR cells at least 1 DNA-binding protein was suppressed, and concomitantly with it several damage-recognition proteins (DRPs) were induced. In addition, gel mobility shift analysis shows that DRPs were overexpressed in CPR cells. These results suggest a potential negative regulation in normal cells that may be important for the induction of DRPs and the emergence of a repair-mediated CPR phenotype.
Department of Biochemistry, Chang Gung Medical College, Taoyuan, Taiwan, China.
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Chao
D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004351:Drug Resistance; D015180:Electrophoresis, Gel, Two-Dimensional; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D002945:Cisplatin