The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
The ubiquitin ligase Nedd4-1 is dispensable for the regulation of PTEN stability and localization
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DOI：
10.1073/pnas.0803233105
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发表时间：
2008-06-24
影响因子：
11.1
通讯作者：
Rotin, Daniela
中科院分区：
文献类型：
--
作者：
Fouladkou, Fatemeh;Landry, Tamara;Rotin, Daniela
PTEN是一种在癌症中经常突变的肿瘤抑制因子。最近的报道暗示Nedd 4 -1作为调节其稳定性和核定位的PTEN的E3泛素连接酶。我们通过使用来源于两个独立产生的小鼠品系的细胞和组织来测试Nedd 4 -1作为PTEN调节剂的生理作用，所述小鼠品系的Nedd 4 -1基因被破坏。野生型和Nedd 4 -1缺陷细胞之间的PTEN稳定性和泛素化是无法区分的，并且不能检测到两种蛋白质之间的相互作用。此外，PTEN亚细胞分布，显示突出的细胞质和细胞核染色，是独立的Nedd 4 -1的存在。最后，PKB/Akt的激活，细胞质PTEN活性的主要下游靶标，以及PTEN反式激活Rad 51启动子的能力，其核功能的量度，不受Nedd 4 -1的损失的影响。总之，我们的结果不能支持Nedd 4 -1作为E3连接酶调节PTEN稳定性和亚细胞定位的作用。
PTEN is a tumor suppressor frequently mutated in cancer. Recent reports implicated Nedd4-1 as the E3 ubiquitin ligase for PTEN that regulates its stability and nuclear localization. We tested the physiological role of Nedd4-1 as a PTEN regulator by using cells and tissues derived from two independently generated strains of mice with their Nedd4-1 gene disrupted. PTEN stability and ubiquitination were indistinguishable between the wild-type and Nedd4-1-deficient cells, and an interaction between the two proteins could not be detected. Moreover, PTEN subcellular distribution, showing prominent cytoplasmic and nuclear staining, was independent of Nedd4-1 presence. Finally, activation of PKB/Akt, a major downstream target of cytoplasmic PTEN activity, and the ability of PTEN to transactivate the Rad51 promoter, a measure of its nuclear function, were unaffected by the loss of Nedd4-1. Taken together, our results fail to support a role for Nedd4-1 as the E3 ligase regulating PTEN stability and subcellular localization.