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J Biol Chem. 2008 Feb 22;283(8):4834-40. Epub 2007 Dec 12.

Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1.

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  • 1Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.

Abstract

The NKX3.1 gene located at 8p21.2 encodes a homeodomain-containing transcription factor that acts as a haploinsufficient tumor suppressor in prostate cancer. Diminished protein expression of NKX3.1 has been observed in prostate cancer precursors and carcinomas. TOPORS is a ubiquitously expressed E3 ubiquitin ligase that can ubiquitinate tumor suppressor p53. Here we report interaction between NKX3.1 and TOPORS. NKX3.1 can be ubiquitinated by TOPORS in vitro and in vivo, and overexpression of TOPORS leads to NKX3.1 proteasomal degradation in prostate cancer cells. Conversely, small interfering RNA-mediated knockdown of TOPORS leads to an increased steady-state level and prolonged half-life of NKX3.1. These data establish TOPORS as a negative regulator of NKX3.1 and implicate TOPORS in prostate cancer progression.

PMID:
18077445
DOI:
10.1074/jbc.M708630200
[PubMed - indexed for MEDLINE]
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