1. ¹Tumor Biology Program, Mayo Foundation and Graduate School, Hilton Building Room 806, 200 First Street, SW Rochester, MN 55905, USA
2. ²Division of Experimental Pathology, Mayo Foundation and Graduate School, Hilton Building Room 806, 200 First Street, SW Rochester, MN 55905, USA

Correspondence: CD James, Laboratory Medicine and Pathology, Mayo Foundation Clinic, 200 First Street, SW, Hilton Building Room 80-D, Rochester, USA. E-mail: james.david@mayo.edu

Received 17 November 2004; Accepted 6 January 2005; Published online 14 February 2005.

Abstract

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