Activity-based ubiquitin-specific protease (USP) profiling of virus-infected and malignant human cells.

Journal article

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.

Authors: Ovaa, H; Kessler, B; Rolén, U; Galardy, P; Ploegh, H

• Publication status: Published
• Journal: Proceedings of the National Academy of Sciences of the United States of America
• Volume: 101
• Issue: 8
• Pages: 2253-2258
• Publication date: 2004-02-01
• DOI: 10.1073/pnas.0308411100
• EISSN: 1091-6490
• ISSN: 0027-8424
• Language: English
• Keywords: Humans; T-Lymphocytes; Cell Line; Cell Line, Tumor; Mass Spectrometry; B-Lymphocytes; Endopeptidases; Ubiquitin Thiolesterase