ZNF143 activates gene expression in response to DNA damage and binds to cisplatin-modified DNA.
We have identified a cisplatin-inducible gene, the mitochondrial ribosomal protein S11 (MRP S11) gene, by means of mRNA differential display. Functional analysis of the MRP S11 promoter showed that a Staf binding site in the promoter is required for both basal promoter activity and cisplatin-inducible activity. We also found that Staf binding activity is significantly increased in nuclear extracts from cells treated with cisplatin. ZNF 143 and ZNF 76 are human homologues of the Xenopus transcriptional activator, Staf. ZNF 143 expression is induced by cisplatin but ZNF 76 expression is not. However, ZNF 143 expression is not induced by transplatin, which is clinically ineffective. ZNF143 is an inducible gene by other DNA damaging agents such as gamma-irradiation, etoposide and adriamycin. ZNF 143 also binds preferentially to cisplatin-modified DNA. These results suggest that ZNF 143 participates in cellular responses to DNA damage.
Department of Molecular Biology, University of Occupational and Environmental Health, School of Medicine, Fukuoka, Japan.
Hiroshi
H
Ishiguchi
Hiroto
H
Izumi
Takayuki
T
Torigoe
Yoichiro
Y
Yoshida
Hiroshi
H
Kubota
Sadatoshi
S
Tsuji
Kimitoshi
K
Kohno
D000970:Antineoplastic Agents / Q000009:adverse effects; D001483:Base Sequence; D002945:Cisplatin / Q000009:adverse effects; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D024101:Mitochondrial Proteins / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D015534:Trans-Activators / Q000494:pharmacology*; D014158:Transcription, Genetic; D029867:Xenopus Proteins; D016335:Zinc Fingers
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C489738:MRPS11 protein, human; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D012269:Ribosomal Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; C114253:ZNF143 protein, human; C491943:znf143 protein, Xenopus; D002945:Cisplatin