Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells.
The family of ubiquitin (Ub)-specific proteases (USP) removes Ub from Ub conjugates and regulates a variety of cellular processes. The human genome contains many putative USP-encoding genes, but little is known about USP tissue distribution, pattern of expression, activity, and substrate specificity. We have used a chemistry-based functional proteomics approach to identify active USPs in normal, virus-infected, and tumor-derived human cells. Depending on tissue origin and stage of activation/differentiation, different USP activity profiles were revealed. The activity of specific USPs, including USP5, -7, -9, -13, -15, and -22, was up-regulated by mitogen activation or virus infection in normal T and B lymphocytes. UCH-L1 was highly expressed in tumor cell lines of epithelial and hematopoietic cell origin but was not detected in freshly isolated and mitogen-activated cells. Up-regulation of this USP was a late event in the establishment of Epstein-Barr virus-immortalized lymphoblastoid cell lines and correlated with enhanced proliferation, suggesting a possible role in growth transformation.
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Huib
H
Ovaa
Benedikt M
BM
Kessler
Ulrika
U
Rolén
Paul J
PJ
Galardy
Hidde L
HL
Ploegh
Maria G
MG
Masucci
D001402:B-Lymphocytes / Q000201:enzymology* / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D013601:T-Lymphocytes / Q000201:enzymology* / Q000821:virology; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases
D010450:Endopeptidases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases