Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

Lee D.; Park S.-J.; Sung K.S.; Park J.; Lee S.B.; Park S.-Y.; Lee H.J.; Ahn J.-W.; Choi S.J.; Lee S.-G.; Kim S.-H.; Kim D.-H.; Kim J.; Kim Y.; Choi C.Y.

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Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

机译：Mdm2与Ras效应器NORE1相关联以诱导癌蛋白HIPK1的降解

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The Ras effector NORE1 is frequently silenced in primary adenocarcinomas, although the significance of this silencing for tumorigenesis is unclear. Here we show that NORE1 induces polyubiquitination and proteasomal degradation of oncoprotein HIPK1 by facilitating its interaction with the Mdm2 E3 ubiquitin ligase. Endogenous HIPK1 is stabilized in Nore1-deficient mouse embryonic fibroblasts, and depletion of HIPK1 in NORE1-silenced lung adenocarcinoma cells inhibits anchorage-independent cell growth and tumour formation in nude mice. These findings indicate that the control of HIPK1 stability by Mdm2-NORE1 has a major effect on cell behaviour, and epigenetic inactivation of NORE1 enables adenocarcinoma formation in vivo through HIPK1 stabilization.

机译：Ras效应蛋白NORE1在原发性腺癌中经常沉默，尽管这种沉默对肿瘤发生的意义尚不清楚。在这里，我们显示NORE1通过促进其与Mdm2 E3泛素连接酶的相互作用来诱导癌蛋白HIPK1的多泛素化和蛋白酶体降解。内源性HIPK1在Nore1缺陷小鼠胚胎成纤维细胞中稳定，而NORE1沉默的肺腺癌细胞中HIPK1的消耗会抑制裸鼠的锚定非依赖性细胞生长和肿瘤形成。这些发现表明，Mdm2-NORE1对HIPK1稳定性的控制对细胞行为具有重大影响，而NORE1的表观遗传失活则可以通过HIPK1稳定作用在体内形成腺癌。

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《EMBO reports》 |2012年第2期|共7页
作者
Lee D.; Park S.-J.; Sung K.S.; Park J.; Lee S.B.; Park S.-Y.; Lee H.J.; Ahn J.-W.; Choi S.J.; Lee S.-G.; Kim S.-H.; Kim D.-H.; Kim J.; Kim Y.; Choi C.Y.;
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正文语种 eng
中图分类分子生物学;
关键词
homeodomaininteracting protein kinase 1; Novel Ras effector 1; oncogene; RASSF5; tumorigenesis;

机译：同源域相互作用蛋白激酶1;小说Ras效应子1;致癌基因;RASSF5;肿瘤发生;

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2. Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1 [J] . Lee D., Park S.-J., Sung K.S., EMBO reports . 2012,第2期

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Mdm2 associates with Ras effector NORE1 to induce the degradation of oncoprotein HIPK1

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