Research Institute, National Center for Geriatrics and Gerontology, 35 Gengo, Moriokacho, Obu, Aichi 474-8511, Japan.
Mol Cell Biol. 2011 May;31(10):1997-2009. doi: 10.1128/MCB.01424-10. Epub 2011 Mar 14.
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.
RNA 结合蛋白 Hzf（造血锌指）在小脑浦肯野细胞和脂肪细胞中的 mRNA 翻译中发挥重要作用。我们与其他人一起报告称，Hzf 基因的表达受抑癌蛋白 p53 的转录调控。我们在这里表明，Hzf 与 HuR 合作调节 p53 的表达。Hzf 和 HuR 均可独立与 p53 mRNA 的 3'非翻译区 (UTR) 相互作用，这有利于 ARF 肿瘤抑制蛋白存在时 p53 mRNA 的细胞质定位。在没有 Hzf 和 HuR 的情况下，p19(ARF) 诱导的 p53 明显减弱，并且细胞因此获得对 p19(ARF)的抗性。因此，这些发现表明，除了抑制 Mdm2 外，p19(ARF)还通过 p53 mRNA 的转录后控制增加 p53 的浓度，并表明 RNA 结合蛋白 Hzf 和 HuR 在 p53 诱导中起关键作用。
