Nuclear HuR accumulation through phosphorylation by Cdk1
Nuclear HuR accumulation through phosphorylation by Cdk1
复制标题
DOI：
10.1101/gad.1645808
复制
发表时间：
2008-07-01
影响因子：
10.5
通讯作者：
Gorospe, Myriam
中科院分区：
文献类型：
--
作者：
Kim, Hyeon Ho;Abdelmohsen, Kotb;Gorospe, Myriam
HuR是一种主要的核RNA结合蛋白，响应于应激和增殖信号而易位至细胞质，在那里它稳定或调节靶mRNA的翻译。在这里，我们提出的证据表明，HuR磷酸化S202的G2期激酶Cdk 1影响其亚细胞分布。HuR特异性磷酸化同步G2期培养物，其细胞质水平增加Cdk 1抑制干预和Cdk 1激活干预下降。与不可磷酸化的点突变HuR（S202 A）的显著细胞质位置一致，使用新型抗磷酸化HuR（S202）抗体显示磷酸化HuR（S202）主要在核中。非磷酸化HuR的增强的细胞质存在与其与14-3-3的结合减少以及其与靶mRNA的结合增强有关。我们的研究结果表明，Cdk 1磷酸化HuR在G2，从而有助于保留在细胞核中与14-3-3和阻碍其转录后功能和抗凋亡的影响。
A predominantly nuclear RNA-binding protein, HuR translocates to the cytoplasm in response to stress and proliferative signals, where it stabilizes or modulates the translation of target mRNAs. Here, we present evidence that HuR phosphorylation at S202 by the G2-phase kinase Cdk1 influences its subcellular distribution. HuR was specifically phosphorylated in synchronous G2-phase cultures; its cytoplasmic levels increased by Cdk1-inhibitory interventions and declined in response to Cdk1-activating interventions. In keeping with the prominently cytoplasmic location of the nonphosphorylatable point mutant HuR(S202A), phospho-HuR(S202) was shown to be predominantly nuclear using a novel anti-phospho-HuR(S202) antibody. The enhanced cytoplasmic presence of unphosphorylated HuR was linked to its decreased association with 14-3-3 and to its heightened binding to target mRNAs. Our findings suggest that Cdk1 phosphorylates HuR during G2, thereby helping to retain it in the nucleus in association with 14-3-3 and hindering its post-transcriptional function and anti-apoptotic influence.