USP32 is an active, membrane-bound ubiquitin protease overexpressed in breast cancers.
USP32, on chromosomal band 17q23.1-17q23.2, is a highly conserved but uncharacterized gene that gave rise during evolution to a well-known hominoid-specific proto-oncogene, USP6. We investigated the expression profile of USP32 in human tissues and examined its functions to gain insight into this novel member of the well-conserved ubiquitination system. We detected ubiquitous USP32 expression across tissues and confirmed the predicted deubiquitination function owing to the presence of conserved peptidase signature aspargine, cysteine, histidine, and aspartic acid domains of ubiquitin-specific proteases. A Golgi localization of GFP-fused USP32 was detected by fluorescent protection assay and BODIPY-TR staining. In addition, stable silencing of USP32 caused a significant decrease in the proliferation and migration rate of cells. Based on these and the fact that USP32 maps to 17q23, which is commonly amplified in breast cancers, we analyzed USP32 expression in breast cancer cells. We detected high expression of USP32 in 50% (9 of 18) of breast cancer cell lines and 22% (9 of 41) of primary breast tumors compared to mammary epithelial cells. In summary, we report the preliminary characterization of this novel deubiquitinating enzyme on 17q23 and demonstrate its functional role in the ubiquitin system and its potential involvement in tumorigenesis.
Akhavantabasi
Shiva
S
Department of Biological Sciences, Inonu Bulvari, M.E.T.U, Ankara, Turkey.
Akman
Hesna B
HB
Sapmaz
Aysegul
A
Keller
Jennifer
J
Petty
Elizabeth M
EM
Erson
Ayse E
AE
D000595:Amino Acid Sequence; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D010450:Endopeptidases / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D000090063:Proto-Oncogene Mas; D017386:Sequence Homology, Amino Acid; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D064570:Ubiquitin-Specific Proteases; D015854:Up-Regulation
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C431363:USP10 protein, human; D010450:Endopeptidases; D043222:Ubiquitin Thiolesterase; D064570:Ubiquitin-Specific Proteases