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Expression and Localization of the CDC34 Ubiquitin-conjugating Enzyme in Pediatric Acute Lymphoblastic Leukemia¹

Department of Pediatrics, Texas Children’s Cancer Center, Baylor College of Medicine, Houston, Texas 77030 [E. E., D. P., J. F. M., S. E. P.]; The Breast Center, Baylor College of Medicine, Houston, Texas 77030 [S. K. M.]; and Department of Pediatrics, University of California at San Diego Medical Center, San Diego, California 92103 [M. B. D., A. L. Y.]

Ubiquitin-dependent protein degradation impacts many cellular processes.However, 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 fold higher level (P < 0.001) in pediatric T cell than in pre-B-cell acute lymphoblastic leukemia (ALL) before treatment in two independent patient sets. The level of CDC34 mRNA was similar in both types of leukemia. CDC34 expression levels in normal resting T cells, B cells and activated T lymphocytes 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 difference in expression was not attributable to mutation or associated with altered CDC34 stability. Immunohistochemistry and cellular fractionation reveals a heterogeneous CDC34 expression pattern including cells containing primarily cytoplasmic or nuclear protein. Thus, a feature of pediatric T-cell ALL is posttranscriptional up-regulation and heterogeneous localization of the human CDC34 UBC.

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