c-myc overexpression activates alternative pathways for intracellular proteolysis in lymphoma cells

Burkitt's lymphoma (BL) is a highly malignant B-cell tumour characterized b y chromosomal translocations that constitutively activate the c-myc oncogen e. Here we show that BL cells are resistant to apoptosis and do not accumul ate ubiquitin conjugates in response to otherwise toxic doses of inhibitors of the proteasome. Deubiquitinating enzymes and the cytosolic subtilisin-l ike protease tripeptidylpeptidase II are upregulated in BLs, and could be r apidly induced by the overexpression of c-myc in normal B cells carrying oe strogen driven recombinant Epstein-Barr virus. Apoptosis was induced by inh ibiting tripeptidylpeptidase II, suggesting that the activity of this prote ase may be required for the survival of BL cells. We thus show that there i s a regulatory link between c-myc activation and changes in proteolysis tha t may affect malignant transformation.