title: PARP1 gene expression is downregulated by knockdown of PARG gene.
abstract: Poly(ADP-ribosyl)ation is a modification of nuclear proteins that regulates DNA replication, repair and transcription. In order to investigate the biological effects of degradation of poly(ADP-ribose), knockdown of the poly(ADP-ribose) glycohydrolase (PARG) gene was performed by introducing a short interfering RNA (siRNA)-pool into HeLa S3 cells. Notably, poly(ADP-ribosyl)ated proteins did not accumulate in the cells. Western blotting, quantitative RT-PCR analysis and a transient transfection assay revealed that poly(ADP-ribose) polymerase 1 (PARP1) gene/protein expression and its promoter activity were reduced in the PARG knockdown cells. These results suggest that the amount of poly(ADP-ribose) in a cell is regulated under the control of PARP1/PARG gene expression balance. Furthermore, in this study, we showed that PARG-siRNA enhanced cell death induced by staurosporine (STS). Thus, we propose a PARG-siRNA utilizing gene-therapy for cancer treatment.
authors: Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda-shi, Chiba-ken 278-8510, Japan. uchiumi@rs.noda.tus.ac.jp
authors: Fumiaki
authors: F
authors: Uchiumi
authors: Takeshi
authors: T
authors: Watanabe
authors: Ryo
authors: R
authors: Ohta
authors: Hideaki
authors: H
authors: Abe
authors: Sei-Ichi
authors: S
authors: Tanuma
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D006026:Glycoside Hydrolases / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D008769:Methylnitronitrosoguanidine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase; D019311:Staurosporine