Characterization of porcine p53 and its regulation by porcine Mdm2
Characterization of porcine p53 and its regulation by porcine Mdm2
复制标题
猪 p53 的表征及其受猪 Mdm2 的调控
DOI：
10.1016/j.gene.2020.144699
复制
发表时间：
2020-07-20
期刊：
影响因子：
3.5
通讯作者：
Bai，Rulan
中科院分区：
文献类型：
--
作者：
Lang，Yue;Yu，Cuilian;Bai，Rulan
猪越来越被认为是研究许多人类疾病的相关模型。然而，在猪中，参与人类疾病的许多关键分子的功能和调节并没有得到很好的表征，包括突出的肿瘤抑制因子p53，一种参与各种抗增殖过程的转录因子。在这项研究中，我们系统地描述了猪p53（p-p53）的转录活性和调控的E3连接酶Mdm 2，与人p53（h-p53）的比较。p-p53与h-p53高度同源，N-末端区域显示相对差异。p-p53对多种已知靶基因表现出与h-p53相当的转录活性，并且受到人和猪Mdm 2（h-/p-Mdm 2）的泛素化和降解。利用靶向h-Mdm 2的化合物Nutlin-3和蛋白RPL 11抑制p-Mdm 2对p-p53的负面作用。这些结果表明，p-p53的转录活性和调节非常类似于h-p53，并且所开发的针对h-p53通路的药物可用于猪中p53相关过程和疾病的研究。
Pigs have been increasingly recognized as a relevant model for studying many human diseases. However, functions and regulations of numerous critical molecules involved in human diseases are not well characterized in pigs, including the prominent tumor suppressor p53, a transcription factor involved in various anti-proliferative processes. In this study, we systematically characterized porcine p53 (p-p53) in its transcriptional activity and regulation by the E3 ligase Mdm2, in comparison with that of human p53 (h-p53). p-p53 is highly homologous to h-p53 with the N-terminal region showing relative divergence. p-p53 exhibits a comparable transcriptional activity to that of h-p53 towards a diverse range of known target genes, and is subject to ubiquitination and degradation by both human and porcine Mdm2 (h-/p-Mdm2). Utilization of the h-Mdm2 targeting compound Nutlin-3 and protein RPL11 inhibits the negative effect of p-Mdm2 on p-p53. These results suggest that the transcription activity and regulation of p-p53 is very similar to that of h-p53, and that the developed agents targeting the h-p53 pathway could be used in the study of p53 related processes and diseases in pigs.