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

Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2253-8. doi: 10.1073/pnas.0308411100.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / virology
  • Cell Line
  • Cell Line, Tumor
  • Endopeptidases / metabolism*
  • Humans
  • Mass Spectrometry
  • T-Lymphocytes / enzymology*
  • T-Lymphocytes / virology
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7
  • Ubiquitin-Specific Proteases

Substances

  • Endopeptidases
  • USP7 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Peptidase 7
  • Ubiquitin-Specific Proteases