title: ECop (EGFR-coamplified and overexpressed protein), a novel protein, regulates NF-kappaB transcriptional activity and associated apoptotic response in an IkappaBalpha-dependent manner.
abstract: In the present study, we describe the function of a novel protein, ECop (EGFR-Coamplified and overexpressed protein), in the regulation of NF-kappaB activity. Ectopic expression of ECop increases NF-kappaB transcriptional activity by promoting nuclear translocation and DNA binding of NF-kappaB, and ECop-induced NF-kappaB activation confers cellular resistance to apoptotic challenge. In ECop knockdown cells, NF-kappaB transcriptional activity is suppressed due to delayed IkappaBalpha degradation, which results in a delayed nuclear translocation as well as decreased DNA binding of NF-kappaB. Suppression of NF-kappaB activation by ECop knockdown increases cellular susceptibility to apoptosis. These results suggest that ECop is a key regulator of NF-kappaB signaling, and that high-level, amplification-mediated ECop expression, such as that occurring in tumors with amplified EGFR, could contribute to resistance to apoptosis.
authors.affiliation: Tumor Biology Program, Mayo Foundation and Graduate School, Hilton Building Room 806, 200 First Street, SW Rochester, MN 55905, USA.
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.forename: C D
authors.initials: CD
authors.lastname: James
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D004247:DNA / Q000378:metabolism; D005784:Gene Amplification; D005786:Gene Expression Regulation; D018773:Genes, erbB-1; D006801:Humans; D007668:Kidney / Q000166:cytology; D016328:NF-kappa B / Q000494:pharmacology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000494:pharmacology*; D014158:Transcription, Genetic
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors; C500380:VOPP1 protein, human; D004247:DNA