Expression and localization of the CDC34 ubiquitin-conjugating enzyme in pediatric acute lymphoblastic leukemia.
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.
Eliseeva
E
E
Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Pati
D
D
Diccinanni
M B
MB
Yu
A L
AL
Mohsin
S K
SK
Margolin
J F
JF
Plon
S E
SE
D064173:Anaphase-Promoting Complex-Cyclosome; D002051:Burkitt Lymphoma / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002455:Cell Division / Q000502:physiology; D002648:Child; D015973:Gene Expression Regulation, Leukemic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D008025:Ligases / Q000235:genetics* / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000502:physiology; D009154:Mutation / Q000502:physiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases; D014452:Ubiquitins / Q000378:metabolism*
D012333:RNA, Messenger; D014452:Ubiquitins; C577447:CDC34 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044767:Ubiquitin-Protein Ligases; D008025:Ligases