The isopeptidase USP2a protects human prostate cancer from apoptosis.


Journal Article

Deubiquitinating enzymes can prevent the destruction of protein substrates prior to proteasomal degradation. The ubiquitin-specific protease 2a (USP2a) deubiquitinates the antiapoptotic proteins Fatty Acid Synthase and Mdm2. Here, we show that when USP2a is overexpressed in nontransformed cells, it exhibits oncogenic behavior both in vitro and in vivo and prevents apoptosis induced by chemotherapeutic agents. Notably, USP2a silencing in several human cancer cell lines results in apoptosis. Gene set enrichment analysis, which focuses on groups of genes sharing biological function or regulatory pathways, was done on microarray expression data from human prostate cancers. The cell death-related gene set, as well as a selected cluster of validated p53 target genes, were significantly enriched in the low USP2a expression group of tumors. Conversely, genes implicated in fatty acid metabolism were significantly associated with tumors expressing high USP2a (44%). The expression profile analysis is consistent with the effects of USP2a on its known targets, i.e., Fatty Acid Synthase and Mdm2, defining a subset of prostate tumors resistant to apoptosis. USP2a thus represents a therapeutic target in prostate cancer.

Full Text

Cited Authors

  • Priolo, C; Tang, D; Brahamandan, M; Benassi, B; Sicinska, E; Ogino, S; Farsetti, A; Porrello, A; Finn, S; Zimmermann, J; Febbo, P; Loda, M

Published Date

  • September 1, 2006

Published In

Volume / Issue

  • 66 / 17

Start / End Page

  • 8625 - 8632

PubMed ID

  • 16951176

Pubmed Central ID

  • 16951176

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-06-1374


  • eng

Conference Location

  • United States