title: RPAP3 enhances cytotoxicity of doxorubicin by impairing NF-kappa B pathway.
abstract: Activation of anti-apoptotic gene transcription by NF-κB (nuclear factor-kappa B) has been reported to be linked with a resistance of cancer cells against chemotherapy. NEMO (NF-κB essential modulator) interacts with a number of proteins and modulates the activity of NF-κB pathway. In this study, we revealed that RPAP3 (RNA polymerase II-associated protein 3) possesses an activity to bind with NEMO and to inhibit the ubiquitination of NEMO and that RPAP3 enhances doxorubicin-induced cell death in breast cancer cell line T-47D through the marked impairment of NF-κB pathway. These results indicate that RPAP3 may be a novel modulator of NF-κB pathway in apoptosis induced by anti-cancer chemotherapeutic agents.
authors.affiliation: Department of Pharmacology, Graduate School of Dentistry, Osaka University, Suita, Osaka, Japan.
authors.forename: Kana
authors.initials: K
authors.lastname: Shimada
authors.forename: Makio
authors.initials: M
authors.lastname: Saeki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Egusa
authors.forename: Sho
authors.initials: S
authors.lastname: Fukuyasu
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yura
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamisaki
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D054875:Ubiquitination
chemical_list: D000903:Antibiotics, Antineoplastic; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C491731:IKBKG protein, human; D016328:NF-kappa B; C472351:RPAP3 protein, human; D004317:Doxorubicin; D051550:I-kappa B Kinase