Cooperative Role of the RNA-Binding Proteins Hzf and HuR in p53 Activation
Cooperative Role of the RNA-Binding Proteins Hzf and HuR in p53 Activation
复制标题
DOI：
10.1128/mcb.01424-10
复制
发表时间：
2011-05-01
影响因子：
5.3
通讯作者：
Sugimoto, Masataka
中科院分区：
文献类型：
--
作者：
Nakamura, Hideaki;Kawagishi, Hiroyuki;Sugimoto, Masataka
在小脑浦肯野细胞和脂肪细胞中，RNA结合蛋白Hzf(造血锌指)在mRNA翻译中起重要作用。我们和其他人一起报道了Hzf基因的表达受p53肿瘤抑制蛋白的转录调控。我们在这里表明，HZF通过与HUR协同调节P53的表达。HZF和HUR独立地与P53基因的3‘非翻译区相互作用，在ARF肿瘤抑制蛋白存在的情况下，促进了P53基因的细胞质定位。在没有HZF和HUR的情况下，p19(ARF)对p53的诱导显著减弱，从而使细胞对p19(ARF)产生耐药性。因此，这些发现表明，除了对MDM2的抑制外，p19(ARF)还通过转录后控制P53 mRNA来增加P53的浓度，并提示RNA结合蛋白Hzf和Hur在P53诱导中发挥关键作用。
The RNA-binding protein Hzf (hematopoietic zinc finger) plays important roles in mRNA translation in cerebellar Purkinje cells and adipocytes. We along with others have reported that the expression of the Hzf gene is transcriptionally regulated by the p53 tumor suppressor protein. We show here that Hzf regulates p53 expression in cooperation with HuR. Hzf and HuR independently interact with the 3' untranslated region (UTR) of p53 mRNA, which facilitates the cytoplasmic localization of p53 mRNA in the presence of the ARF tumor suppressor protein. In the absence of Hzf and HuR, p53 induction by p19(ARF) is significantly attenuated, and the cells consequently acquire resistance to p19(ARF). Thus, these findings demonstrate that in addition to Mdm2 inhibition, p19(ARF) increases the concentration of p53 through posttranscriptional control of p53 mRNA and suggest critical roles for the RNA-binding proteins Hzf and HuR in p53 induction.