Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1
Ubiquitination by TOPORS regulates the prostate tumor suppressor NKX3.1
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DOI：
10.1074/jbc.m708630200
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发表时间：
2008-02-22
影响因子：
4.8
通讯作者：
Bieberich, Charles J.
中科院分区：
文献类型：
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作者：
Guan, Bin;Pungaliya, Pooja;Bieberich, Charles J.
位于8p21.2的NKX3.1基因编码一个含有同源结构域的转录因子，该转录因子在前列腺癌中作为单倍体充分的肿瘤抑制因子。在前列腺癌前体和癌中观察到NKX3.1蛋白表达减少。TOPORS是一种广泛表达的E3泛素连接酶，可以泛素化肿瘤抑制基因p53。在这里，我们报告NKX3.1和TOPORS之间的相互作用。NKX3.1可以在体外和体内被TOPORS遍在化，TOPORS的过表达导致前列腺癌细胞中NKX3.1蛋白酶体降解。相反，小干扰RNA介导的TOPORS敲低导致NKX3.1的稳态水平增加和半衰期延长。这些数据确立了TOPORS作为NKX3.1的负调节因子，并暗示TOPORS在前列腺癌进展中。
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.