title: PARP-1 regulates the expression of caspase-11.
abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a multifunctional enzyme that regulates DNA repair, cell death and transcription of inflammatory proteins. In the present study, we present evidence that PARP-1 regulates the expression of caspase-11 following lipopolysaccharide (LPS) stimulation. Knockdown of PARP-1 suppressed the LPS-induced expression of caspase-11 at both mRNA and protein levels as well as caspase-11 promoter activity. Importantly, PARP-1 was recruited to the caspase-11 promoter region containing predicted nuclear factor (NF)-κB-binding sites when examined by chromatin immunoprecipitation assay. However, knockdown of PARP-1 did not suppress the expression of caspase-11 induced by interferon-γ that activates signal transducer and activator of transcription 1 but not NF-κB. PARP-1 enzymatic activity was not required for the caspase-11 upregulation since pharmacological inhibitors of PARP-1 did not suppress the induction of caspase-11. Our results suggest that PARP-1, as a transcriptional cofactor for NF-κB, regulates the induction of caspase-11 at a transcriptional level.
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 143-747, Republic of Korea.
authors.forename: Lang
authors.initials: L
authors.lastname: Yoo
authors.forename: Seokheon
authors.initials: S
authors.lastname: Hong
authors.forename: Ki Soon
authors.initials: KS
authors.lastname: Shin
authors.forename: Shin Jung
authors.initials: SJ
authors.lastname: Kang
mesh_terms: D000818:Animals; D020169:Caspases / Q000235:genetics*; D053471:Caspases, Initiator; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D007371:Interferon-gamma; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator