title: Protein kinase Cη activates NF-κB in response to camptothecin-induced DNA damage.
abstract: The nuclear factor κB (NF-κB) family of transcription factors participates in the regulation of genes involved in innate- and adaptive-immune responses, cell death and inflammation. The involvement of the Protein kinase C (PKC) family in the regulation of NF-κB in inflammation and immune-related signaling has been extensively studied. However, not much is known on the role of PKC in NF-κB regulation in response to DNA damage. Here we demonstrate for the first time that PKC-eta (PKCη) regulates NF-κB upstream signaling by activating the IκB kinase (IKK) and the degradation of IκB. Furthermore, PKCη enhances the nuclear translocation and transactivation of NF-κB under non-stressed conditions and in response to the anticancer drug camptothecin. We and others have previously shown that PKCη confers protection against DNA damage-induced apoptosis. Our present study suggests that PKCη is involved in NF-κB signaling leading to drug resistance.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, The Cancer Research Center, Ben-Gurion University of the Negev, Israel.
authors.forename: Hadas
authors.initials: H
authors.lastname: Raveh-Amit
authors.forename: Naama
authors.initials: N
authors.lastname: Hai
authors.forename: Noa
authors.initials: N
authors.lastname: Rotem-Dai
authors.forename: Galit
authors.initials: G
authors.lastname: Shahaf
authors.forename: Jacob
authors.initials: J
authors.lastname: Gopas
authors.forename: Etta
authors.initials: E
authors.lastname: Livneh
mesh_terms: D021581:Active Transport, Cell Nucleus; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004249:DNA Damage; D019008:Drug Resistance, Neoplasm; D006801:Humans; D016328:NF-kappa B / Q000819:agonists* / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; C498143:RELA protein, human; D051996:Transcription Factor RelA; C081975:protein kinase C eta; D011493:Protein Kinase C; D002166:Camptothecin