Expression and localization of the CDC34 ubiquitin-conjugating enzyme in pediatric acute lymphoblastic leukemia

Ubiquitin-dependent protein degradation impacts many cellular processes. Ho wever, the regulation of ubiquitin-conjugating enzymes (UBCs) in cancer is unknown. We find that the human CDC34 UBC protein is expressed at a 3-4 fol d higher level (P < 0.001) in pediatric T cell than in pre-B-cell acute lym phoblastic leukemia (ALL) before treatment in two independent patient sets. The level of CDC34 mRNA was similar in both types of leukemia. CDC34 expre ssion levels in normal resting T cells, B cells, and activated T lymphocyte s was comparable with pre-B-cell ALL. CDC34 protein (but not mRNA) was also increased in T-cell ALL compared with pre-B-cell ALL cell lines. The diffe rence in expression was not attributable to mutation or associated with alt ered CDC34 stability. Immunohistochemistry and cellular fractionation revea ls a heterogeneous CDC34 expression pattern including cells containing prim arily cytoplasmic or nuclear protein. Thus, a feature of pediatric T-cell A LL is posttranscriptional up-regulation and heterogeneous localization of t he human CDC34 UBC.