Published in Cancer Detection and Prevention 2002; 26(2).

Association of a new c-Cbl related protein with the very first stages of apoptosis induction

Laurent Corsois MD a, Brigitte Quatannens a, Patrick Dumont a, Marc Aumercierl PhD a, Marie-Paule Defresne MD b Daniel C.L. Regnier MD, PhD a

aLaboratory of Molecular Oncology, CNRS-UMR 8526, Institut de Biologie de Lille, Institut Pasteur de Lille, l, rue Calmette, B.P. 447, 59021 Lille Cedex, France b Laboratory of Pathologucal Anatomy, CHU-B35, B-4000 Liege, Belgium

Accepted 27 September 2001

This study investigates the involvement of the c-cbl proto-oncogene during the first stages of the apoptotic process. We have already shown that a c-Cbl aptotosis-related protein of 90 kDa (CARP 90) is detected very rapidly in the cytoplasm as well as in the nucleus of murine thymocytes after hydrocortisone (HC) treatment. We report here that this protein appeared as well after in vivo treatment of mice by γ-irradiation or injection of anti-CD3 monoclonal antibody, two potent thymic apoptosis inductors, providing a close relationship between the occurrence of apoptosis and the appearance of CARP 90. We showed that CARP 90 and pl2Ocbl share numerous epitopes strikingly suggesting that CARP 90 is coded by c-cbl. In addition, KO mice do not sustain CARP 90 appearance. We finally showed that CARP 90 contains N- and C-terminal end epitopes of pl2Ocbl, which suggests that CARP 90 is an alternative spliced form of c-cbl. This protein was also observed under γ-irradiation in tissues of different origin, which enlarges the physiological significance of this phenomenon. The very rapid CARP 90 appearance under apoptotic conditions in the nucleus of cells originating in different tissues makes this protein if not a possible new actor of the apoptic process at least an interesting marker of this process.

KEY WORDS: Hydrocortisone, y-Irradiation, Anti-CD3 monoclonal antibody, Thymus.