Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1

被引：40

作者：

Guan, Bin ^{[1
]}

Pungaliya, Pooja ^{[2
,3
]}

Li, Xiang ^{[1
]}

Uquillas, Carlos ^{[1
]}

Mutton, Laura N. ^{[1
]}

Rubin, Eric H. ^{[2
,3
]}

Bieberich, Charles J. ^{[1
,4
]}

机构：

[1] Univ Maryland, Dept Biol Sci, Baltimore, MD 21250 USA

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Inst Canc, New Brunswick, NJ 08901 USA

[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Inst Canc, New Brunswick, NJ 08901 USA

[4] Univ Maryland, Sch Med, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 08期

关键词：

D O I：

10.1074/jbc.M708630200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The NKX3.1 gene located at 8p21.2 encodes a homeodomain-containing transcription factor that acts as a haploin sufficient 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.

引用

页码：4834 / 4840

页数：7

共 51 条

[1] Deletion, methylation, and expression of the NKX3.1 suppressor gene in primary human prostate cancer [J].