ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes.
Zinc-finger protein 143 (ZNF143) is a human homolog of Xenopus transcriptional activator staf that is involved in selenocystyl tRNA transcription. We previously showed that ZNF143 expression is induced by treatment with DNA-damaging agents and that it preferentially binds to cisplatin-modified DNA. In this study, the potential function of ZNF143 was investigated. ZNF143 was overexpressed in cisplatin-resistant cells. ZNF143 knockdown in prostate cancer caused increased sensitivity for cisplatin, but not for oxaliplatin, etoposide and vincristine. We also showed that ZNF143 is associated with tumor suppressor gene product p73 but not with p53. p73 could stimulate the binding of ZNF143 to both ZNF143 binding site and cisplatin-modified DNA, and modulate the function of ZNF143. We provide a direct evidence that both Rad51 and flap endonuclease-1 are target genes of ZNF143 and overexpressed in cisplatin-resistant cells. Taken together, these experiments demonstrate that an interplay of ZNF143, p73 and ZNF143 target genes is involved in DNA repair gene expression and cisplatin resistance.
Wakasugi
T
T
Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Izumi
H
H
Uchiumi
T
T
Suzuki
H
H
Arao
T
T
Nishio
K
K
Kohno
K
K
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D017931:DNA Primers; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D000970:Antineoplastic Agents; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D015534:Trans-Activators; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; C114253:ZNF143 protein, human; D002945:Cisplatin