RNF43 interacts with NEDL1 and regulates p53-mediated transcription
RNF43 interacts with NEDL1 and regulates p53-mediated transcription
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DOI：
10.1016/j.bbrc.2010.11.082
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发表时间：
2011-01-07
影响因子：
3.1
通讯作者：
Hatakeyama, Shigetsugu
中科院分区：
文献类型：
--
作者：
Shinada, Keisuke;Tsukiyama, Tadasuke;Hatakeyama, Shigetsugu
泛素-蛋白酶体系统在结直肠组织的肿瘤发生中起着至关重要的作用。最近的研究表明，作为结直肠癌的致癌基因的β-连环蛋白的稳定性受到泛素介导的降解的调节。据报道，推定的E3泛素连接酶，RNF 43，在人结直肠癌中高度表达，并且RNF 43促进细胞生长。然而，RNF 43在致癌作用中的参与尚未完全阐明。在这项研究中，我们发现通过使用酵母双杂交筛选RNF 43结合NEDD-4样泛素蛋白连接酶-1（NEDL 1），这增强了p53的促凋亡活性。此外，我们发现RNF 43还与p53相互作用，RNF 43抑制H1299细胞中p53的转录活性，并减弱紫外线照射诱导的细胞凋亡。这些研究结果表明，RNF 43与NEDL 1协同参与结直肠癌的发生，与p53介导的细胞凋亡有关。(C)2010年爱思唯尔公司All rights reserved.
The ubiquitin-proteasomal system plays a crucial role in oncogenesis in colorectal tissues. Recent studies have shown that stability of beta-catenin, which functions as an oncogene for colorectal cancer, is regulated by ubiquitin-mediated degradation. It has been reported that a putative E3 ubiquitin ligase, RNF43, is highly expressed in human colorectal carcinoma and that RNF43 promotes cell growth. However, the involvement of RNF43 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that RNF43 binds to NEDD-4-like ubiquitin-protein ligase-1 (NEDL1), which enhances pro-apoptotic activity by p53. In addition, we found that RNF43 also interacts with p53 and that RNF43 suppresses transcriptional activity of p53 in H1299 cells and attenuates apoptosis induced by ultraviolet irradiation. These findings suggest that RNF43 is associated with p53-mediated apoptosis in collaboration with NEDL1 in colorectal carcinogenesis. (C) 2010 Elsevier Inc. All rights reserved.