¹Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK

Correspondence: Dr S Lain, E-mail: s.lain@dundee.ac.uk

²Contributed equally to this work

Received 18 September 2002; Revised 4 November 2002; Accepted 8 November 2002.

Abstract

The nuclear export inhibitor leptomycin B (LMB) prevents the export of proteins from the nucleus to the cytoplasm, protects p53 from Mdm2-mediated degradation and is a very potent inducer of the p53 transcriptional activity. Here we suggest that LMB can also interfere with the degradation of human Mdm2. In the presence of this drug, we observed two novel forms of this protein: a slow mobility form and an amino-terminal fragment with an apparent molecular mass of 32 kDa. The presence of this 32 kDa band is abolished with proteasome inhibitors, indicating that its appearance could be because of limited processing by the proteasome. These results may be useful in understanding the mechanism of degradation of Mdm2 by the proteasome.