Enhancement of p53 expression in keratinocytes by the bioflavonoid apigenin is associated with RNA-binding protein HuR.
Enhancement of p53 expression in keratinocytes by the bioflavonoid apigenin is associated with RNA-binding protein HuR.
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DOI：
10.1002/mc.20460
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发表时间：
2009-02
影响因子：
4.6
通讯作者：
Pelling, Jill C.
中科院分区：
文献类型：
--
作者：
Tong, Xin;Pelling, Jill C.
我们以前已经报道过，芹菜素是一种天然存在的非致突变黄酮类化合物，它通过稳定p53蛋白的机制增加了野生型P53蛋白在小鼠角质形成细胞308细胞中的表达。我们进一步证明，芹菜素处理308例角化细胞后，P53蛋白水平的升高不是由于P53 mRNA转录增强、mRNA稳定或胞质输出的结果。相反，生物合成标记显示，芹菜素通过促进P53的翻译来增加新生P53蛋白的合成。P53基因3‘-非翻译区富含AU元件(ARE)与芹菜素增加P53翻译的能力有关，研究表明，含有ARE的P53MRNA的3’-UTR融合在荧光素酶报告基因下游。此外，芹菜素处理增加了RNA结合蛋白HUR与内源性P53mRNA的关联水平。芹菜素处理也增加了HUR转位到细胞质中。在308个角质形成细胞中，hUR过表达增强了芹菜素诱导的P53蛋白表达，而siRNA介导的HUR降低抑制了芹菜素诱导的P53蛋白表达和P53的从头翻译。此外，芹菜素处理细胞可诱导p16蛋白表达，而p16蛋白的表达与芹菜素诱导HUR的胞浆定位有关。总之，这些发现表明，除了调节P53蛋白的稳定性外，芹菜素诱导P53蛋白表达的机制之一是通过RNA结合蛋白Hur促进翻译。
We have reported previously that apigenin, a naturally occurring non-mutagenic flavonoid, increased wild type p53 protein expression in the mouse keratinocyte 308 cell line by a mechanism involving p53 protein stabilization. Here we further demonstrated that the increase in p53 protein level induced by apigenin treatment of 308 keratinoyctes was not the result of enhanced transcription, mRNA stabilization or cytoplasmic export of p53 mRNA. Instead, biosynthetic labeling showed that apigenin increased nascent p53 protein synthesis by enhancing p53 translation. The AU-rich element (ARE) within the 3′-untranslated region (UTR) of p53 mRNA was found to be responsible for apigenin’s ability to increase p53 translation, as demonstrated in studies wherein the 3′-UTR of p53 mRNA containing the ARE was fused downstream of a luciferase reporter gene. Furthermore, apigenin treatment increased the level of association of the RNA binding protein HuR with endogenous p53 mRNA. Apigenin treatment also augmented HuR translocation into the cytoplasm. Overexpression of HuR enhanced apigenin-induced p53 protein expression in 308 keratinocytes, whereas siRNA-mediated HuR reduction suppressed apigenin-induced p53 protein expression and de novo translation of p53. Moreover, apigenin treatment of cells induced p16 protein expression, which in turn was correlated with cytoplasmic localization of HuR induced by apigenin. Overall, these findings indicate that, in addition to modulating p53 protein stability, one of the mechanisms by which apigenin induces p53 protein expression is enhancement of translation through the RNA binding protein HuR.
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影响因子：
29.4
作者：
Martinez-Chantar, Maria L.;Vazquez-Chantada, Mercedes;Mato, Jose M.
通讯作者：
Mato, Jose M.
DOI：
10.1111/j.1432-1033.1986.tb09449.x
发表时间：
1986-02-03
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
MATLASHEWSKI, G;BANKS, L;CRAWFORD, L
通讯作者：
CRAWFORD, L
影响因子：
14.9
作者：
Al-Mohanna, Mai A.;Al-Khalaf, Huda H.;Aboussekhra, Abdelilah
通讯作者：
Aboussekhra, Abdelilah
影响因子：
14.9
作者：
Lee HK;Jeong S
通讯作者：
Jeong S
影响因子：
11.4
作者：
Peng, SSY;Chen, CYA;Shyu, AB
通讯作者：
Shyu, AB