The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer.

Abstract	Cellular levels of key regulatory proteins are controlled via ubiquitination and subsequent degradation. Deubiquitinating enzymes or isopeptidases can potentially prevent targeted destruction of protein substrates through deubiquitination prior to proteasomal degradation. However, only one deubiquitinating enzyme to date has been matched to a specific substrate in mammalian cells and shown to functionally modify it. Here we show that the isopeptidase USP2a (ubiquitin-specific protease-2a) interacts with and stabilizes fatty acid synthase (FAS), which is often overexpressed in biologically aggressive human tumors. Further, USP2a is androgen-regulated and overexpressed in prostate cancer, and its functional inactivation results in decreased FAS protein and enhanced apoptosis. Thus, the isopeptidase USP2a plays a critical role in prostate cancer cell survival through FAS stabilization and represents a therapeutic target in prostate cancer.
Authors	Edgard Graner, Dan Tang, Sabrina Rossi, Antonella Baron, Toshiro Migita, Lisa J Weinstein, Mirna Lechpammer, Dieter Huesken, Johann Zimmermann, Sabina Signoretti, Massimo Loda
Journal	Cancer cell (Cancer Cell) Vol. 5 Issue 3 Pg. 253-61 (Mar 2004) ISSN: 1535-6108 [Print] United States
PMID	15050917 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References	Androgens Isoenzymes Multienzyme Complexes RNA, Small Interfering Fatty Acid Synthases Endopeptidases USP2 protein, human Ubiquitin Thiolesterase Cysteine Endopeptidases Proteasome Endopeptidase Complex
Topics	Androgens (metabolism) Animals Chromatography, Affinity Cysteine Endopeptidases (metabolism) Endopeptidases (metabolism) Fatty Acid Synthases (metabolism) Gene Expression Regulation, Enzymologic Gene Expression Regulation, Neoplastic Humans Isoenzymes (metabolism) Male Mass Spectrometry Multienzyme Complexes (metabolism) Prostatic Neoplasms (enzymology) Proteasome Endopeptidase Complex RNA, Small Interfering (metabolism) Rats Ubiquitin Thiolesterase

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