的亚细胞定位vaccinia-related kinase-2 (VRK2)亚型决定了他们对p53肿瘤细胞系稳定性的不同影响。
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布兰科,Klimcakova L,织女星调频,Lazo PA
的亚细胞定位vaccinia-related kinase-2 (VRK2)亚型决定了他们对p53肿瘤细胞系稳定性的不同影响。
2月j . 2006年6月,273 (11):2487 - 504。
- PubMed ID
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16704422 (在PubMed]
- 文摘
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VRK是一个新的未知函数的激酶家族。内生人力vacinia-related激酶2 (VRK2)蛋白质存在于细胞核和细胞溶质,由于可变剪接的508年和397年的两个VRK2消息编码蛋白质氨基酸,分别。VRK2A c端疏水区域,锚的蛋白质在内质网(ER)膜和线粒体,它与calreticulin colocalizes calnexin mitotracker;而VRK2B检测到细胞质和细胞核。VRK2A表示在所有类型的细胞,而VRK2B表达细胞系中VRK1细胞质。两个VRK2亚型有相同的催化n端结构域和使磷酸化p53在Thr18体外独特。p53蛋白的磷酸化反应细胞应力结果的稳定调节其绑定到其他蛋白质。然而,p53磷酸化也发生在没有压力。只有超表达的核VRK2B同种型诱发p53稳定翻译修饰,很大程度上是由于Thr18磷酸化。VRK2B可能发挥作用在控制的结合特异性p53的氨基端transactivation域。 Indeed, the p53 phosphorylated by VRK2B shows a reduction in ubiquitination by Mdm2 and an increase in acetylation by p300. Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells. The relative phosphorylation of Thr18 by VRK2B is similar in magnitude to that induced by taxol, which might use a different signalling pathway. In this context, VRK2B kinase might functionally replace nuclear VRK1. Therefore, these kinases might be components of a new signalling pathway that is likely to play a role in normal cell proliferation.