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

Edgard Graner, Dan Tang, Sabrina Rossi, Antonella Baron, Toshiro Migita, Lisa J. Weinstein, Mirna Lechpammer, Dieter Huesken, Johann Zimmermann, Sabina Signoretti, Massimo Loda

Research output: Contribution to journalArticle

228 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)253-261
Number of pages9
JournalCancer Cell
Volume5
Issue number3
DOIs
StatePublished - Mar 2004
Externally publishedYes

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

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    Graner, E., Tang, D., Rossi, S., Baron, A., Migita, T., Weinstein, L. J., Lechpammer, M., Huesken, D., Zimmermann, J., Signoretti, S., & Loda, M. (2004). The isopeptidase USP2a regulates the stability of fatty acid synthase in prostate cancer. Cancer Cell, 5(3), 253-261. https://doi.org/10.1016/S1535-6108(04)00055-8