Elsevier

Neoplasia

Volume 8, Issue 8, August 2006, Pages 667-676
Neoplasia

Role of Desumoylation in the Development of Prostate Cancer1

https://doi.org/10.1593/neo.06445Get rights and content
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open access

Abstract

SUMO is a novel ubiquitin-like protein that can covalently modify a large number of nuclear proteins. SUMO modification has emerged as an important regulatory mechanism for protein function and localization. Sumoylation is a dynamic process that is mediated by activating (El), conjugating (E2), and ligating (E3) enzymes and is readily reversed by a family of SUMOspecific proteases (SENPs). Since SUMO was discovered 10 years ago, the biologic contribution of this posttranslational modification has remained unclear. In this review, we report that SENP1, a member of the SENP family, is overexpressed in human prostate cancer specimens. The induction of SENP1 is observed with the chronic exposure of prostate cancer cells to androgen and/or interleukin (IL) 6. SENP1 upregulation modulates the transcriptional activity of androgen receptors (ARs) and c-Jun, as well as cyclin D1 expression. Initial in vivo data from transgenic mice indicate that overexpression of SENP1 in the prostate leads to the development of prostatic intraepithelial neoplasia at an early age. Collectively, these studies indicate that overexpression of SENP1 is associated with prostate cancer development.

Keywords

SUMO
Sentrin
SENP
SUMO-specific protease
prostate cancer

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1

This work was supported by the National Institutes of Health (RO1 CA 80089) and the Department of Defense (CDMRP PC040121).