Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anaphase-Promoting Complex-Cyclosome
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Burkitt Lymphoma / enzymology
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Burkitt Lymphoma / pathology
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Burkitt Lymphoma / physiopathology
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Cell Division / physiology
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Child
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Gene Expression Regulation, Leukemic / physiology*
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Humans
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Immunohistochemistry
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Leukemia-Lymphoma, Adult T-Cell / enzymology
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Leukemia-Lymphoma, Adult T-Cell / pathology
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Leukemia-Lymphoma, Adult T-Cell / physiopathology
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Ligases / genetics*
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Ligases / metabolism*
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Lymphocyte Activation / physiology
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Mutation / physiology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / enzymology*
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
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Precursor Cell Lymphoblastic Leukemia-Lymphoma / physiopathology
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RNA, Messenger / metabolism
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Tumor Cells, Cultured / cytology
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Tumor Cells, Cultured / enzymology
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Ubiquitin-Conjugating Enzymes
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Ubiquitin-Protein Ligase Complexes*
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Ubiquitin-Protein Ligases
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Ubiquitins / metabolism*
Substances
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RNA, Messenger
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Ubiquitins
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CDC34 protein, human
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Ubiquitin-Conjugating Enzymes
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Ubiquitin-Protein Ligase Complexes
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Anaphase-Promoting Complex-Cyclosome
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Ubiquitin-Protein Ligases
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Ligases