Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 8625-8632 |
| Number of pages | 8 |
| Journal | Cancer Research |
| Volume | 66 |
| Issue number | 17 |
| DOIs | |
| Publication status | Published - Sep 1 2006 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
The isopeptidase USP2a protects human prostate cancer from apoptosis. / Priolo, Carmen; Tang, Dan; Brahamandan, Mohan; Benassi, Barbara; Sicinska, Ewa; Ogino, Shuji; Farsetti, Antonella; Porrello, Alessandro; Finn, Stephen; Zimmermann, Johann; Febbo, Phillip; Loda, Massinio.
In: Cancer Research, Vol. 66, No. 17, 01.09.2006, p. 8625-8632.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The isopeptidase USP2a protects human prostate cancer from apoptosis
AU - Priolo, Carmen
AU - Tang, Dan
AU - Brahamandan, Mohan
AU - Benassi, Barbara
AU - Sicinska, Ewa
AU - Ogino, Shuji
AU - Farsetti, Antonella
AU - Porrello, Alessandro
AU - Finn, Stephen
AU - Zimmermann, Johann
AU - Febbo, Phillip
AU - Loda, Massinio
PY - 2006/9/1
Y1 - 2006/9/1
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-06-1374
DO - 10.1158/0008-5472.CAN-06-1374
M3 - Article
VL - 66
SP - 8625
EP - 8632
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 17
ER -