1. ¹UMR 8161, Institut de Biologie de Lille, CNRS/Université de Lille 1/Université de Lille 2/Institut Pasteur de Lille, IFR 142, Lille Cedex, France
2. ²Laboratoire de Virologie Moléculaire, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium

Correspondence: Professor Y de Launoit, UMR 8161, Institut de Biologie de Lille, CNRS/Institut Pasteur de Lille/Universités de Lille 1 et Lille 2, 1 rue du Professeur Calmette, Lille Cedex 59021, France. E-mail: yvan.delaunoit@ibl.fr

³Current address: CNRS UMR 6547, Equipe Physiologie Comparée et Endocrinologie Moléculaire, Université Blaise Pascal Clermont II, Campus Universitaire des Cézeaux, 24 Avenue des Landais, Aubière 63177, France.

Received 11 November 2005; Revised 20 April 2006; Accepted 6 June 2006; Published online 10 July 2006.

Abstract

ERM is a member of the ETS transcription factor family. High levels of the corresponding mRNA are detected in a variety of human breast cancer cell lines, as well as in aggressive human breast tumors. As ERM protein is almost undetectable in these cells, high degradation of this transcription factor has been postulated. Here we have investigated whether ERM degradation might depend on the proteasome pathway. We show that endogenous and ectopically expressed ERM protein is short-lived protein and undergoes proteasome-dependent degradation. Deletion mutagenesis studies indicate that the 61 C-terminal amino acids of ERM are critical for its proteolysis and serve as a degradation signal. Although ERM conjugates with ubiquitin, this post-translational modification does not depend on the C-terminal domain. We have used an Ets-responsive ICAM-1 reporter plasmid to show that the ubiquitin–proteasome pathway can affect transcriptional function of ERM. Thus, ERM is subject to degradation via the 26S proteasome pathway, and this pathway probably plays an important role in regulating ERM transcriptional activity.