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ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner

Oncogene volume 24, pages 2495–2502 (2005)Cite this article

Abstract

In the present study, we describe the function of a novel protein, ECop (EGFR-Coamplified and overexpressed protein), in the regulation of NF-κB activity. Ectopic expression of ECop increases NF-κB transcriptional activity by promoting nuclear translocation and DNA binding of NF-κB, and ECop-induced NF-κB activation confers cellular resistance to apoptotic challenge. In ECop knockdown cells, NF-κB transcriptional activity is suppressed due to delayed IκBα degradation, which results in a delayed nuclear translocation as well as decreased DNA binding of NF-κB. Suppression of NF-κB activation by ECop knockdown increases cellular susceptibility to apoptosis. These results suggest that ECop is a key regulator of NF-κB signaling, and that high-level, amplification-mediated ECop expression, such as that occurring in tumors with amplified EGFR, could contribute to resistance to apoptosis.

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Acknowledgements

We thank James D Orth for help with microscopy and Dr Ralf Janknecht for his generous gift of c-Jun plasmid and experimental advice. We also acknowledge Dr Fergus Couch for helpful discussions throughout the development of this study.

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Authors and Affiliations

  1. Tumor Biology Program, Mayo Foundation and Graduate School, Hilton Building Room 806, 200 First Street, SW Rochester, MN, 55905, USA

    S Park & C D James

  2. Division of Experimental Pathology, Mayo Foundation and Graduate School, Hilton Building Room 806, 200 First Street, SW Rochester, MN, 55905, USA

    C D James

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  1. S Park
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  2. C D James
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Correspondence to C D James.

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Supported by NCI grant CA85799 (CDJ)

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Park, S., James, C. ECop (EGFR-Coamplified and overexpressed protein), a novel protein, regulates NF-κB transcriptional activity and associated apoptotic response in an IκBα-dependent manner. Oncogene 24, 2495–2502 (2005). https://doi.org/10.1038/sj.onc.1208496

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