Article abstract
Nature Cell Biology 3, 283 - 288 (2001)
Published online: 10 February 2001 | doi:10.1038/35060076
c-myc overexpression activates alternative pathways for intracellular proteolysis in lymphoma cells
Riccardo Gavioli1,2,4, Teresa Frisan1,4, Simona Vertuani1,2, Georg W. Bornkamm3 & Maria G. Masucci1
Abstract
Burkitt's lymphoma (BL) is a highly malignant B-cell tumour characterized by chromosomal translocations that constitutively activate the c-myc oncogene. Here we show that BL cells are resistant to apoptosis and do not accumulate ubiquitin conjugates in response to otherwise toxic doses of inhibitors of the proteasome. Deubiquitinating enzymes and the cytosolic subtilisin-like protease tripeptidylpeptidase II are upregulated in BLs, and could be rapidly induced by the overexpression of c-myc in normal B cells carrying oestrogen-driven recombinant Epstein–Barr virus. Apoptosis was induced by inhibiting tripeptidylpeptidase II, suggesting that the activity of this protease may be required for the survival of BL cells. We thus show that there is a regulatory link between c-myc activation and changes in proteolysis that may affect malignant transformation.
- Microbiology and Tumor Biology Center, Karolinska Institutet, Box 280, S-171 77 Stockholm, Sweden
- Department of Biochemistry and Molecular Biology, University of Ferrara, 44100 Ferrara, Italy
- GSF Research Centre for Environment and Health, Institute of Molecular Biology and Tumor Genetics, Marchioninistrasse 25, D-81377 Munich, Germany
- These authors contributed equally to this work
Correspondence to: Maria G. Masucci1 e-mail: maria.masucci@mtc.ki.se
