接触突变维持p53的整体构象但破坏了p53与DNA的结合(例如R248W和R273H);而结构/构象突变则显著改变DBD的构象和稳定性(例如R175H、G245S和R249S),均会破坏p53的转录激活活性。R196、R213、R306和R342是p53无义突变的主要位点。虽然大多数癌症患者...
最近有研究 [ 27 ]表明,定位于细胞质中的某些特定类型的p53突变体(R175H、R273H、R273L)可以通过封锁AMPK信号或激活Akt/mTOR信号来获得抑制自噬的新功能。相比之下,在细胞核中定位的其他p53突变体(P151H、R282W)却不能抑制自噬。这些胞质p53突变体通过抑制几种重要的自噬相关蛋白酶,如BECN1、DRAM1和ATG12等,...
With this regard, we found that not only p53-R273H, but also other hotspot mutants, p53-R175H and p53-R248W, significantly inhibited KLF6 expression at both mRNA (Fig. 2a) and protein levels (Fig. 2b), and promoted cell migration (Fig. 2c). In addition, knockdown of endogenous ...
Notably, we found that plakoglobin's tumor suppressive effects were significantly stronger in p53-R175H expressing cells compared to p53-R273H cells. Together, our results indicate that exploring plakoglobin interactions with p53-R175H may be useful for the development ...
However, several of these p53 mutants, including the hotspot mutants R175H and R273H, show a gain of oncogenic function in driving invasion and metastasis.1–3 This novel gain of function is related, at least in part, to the ability of mutant p53 to cause changes in gene expression.4,5...
To test whether mutp53 may also induce Twist1 expression in additional cellular systems, we infected the immortalized WI-38 lung fibroblasts with either p53R175H or p53R273H mutants or with shp53 as a control for the loss of wt-p53 function. Both p53R175H and p53R273H mutants overexpress...
结合型mp53包括p53-r273h,p53-r273c,p53-r248q和p53-r248w。 “结构型mp53”是指与wtp53相比,其三维结构明显被破坏的mp53。结构型mp53包括p53-r175h,p53-g245d,p53-g245s,p53-r249s和p53-r282w。 “人工p53”是指人工改造的p53,人工改造的p53优选示例包括p53融合蛋白,p53片段,p53肽,p53衍生的...
1 为空载体;2 为 wt鄄p53;3 为 R175H鄄p53;4 为 R248W鄄p53;5 为 R273H鄄p53 图 4摇 Western blot 检测 HEK鄄293T 细胞中突变型 p53 对 SASH1 表达的影响 注:a 图为 SASH1 对 HA鄄Tp53 表达的影响;b 图为 SASH1 对 endo鄄Tp53 表达的影响. 0 为空白对照;1 为空载体;2 为 wt鄄 SAS...
The p53 mutants R175H and R273H appear to facilitate cell invasion by interaction with the NRD1 metalloprotease [61], or by modulating MET signalling [62]. Also p53 mutants, by their incorporation in gene promoters containing the SREBP transcription factor can regulate genes in the mevalonate ...
suggested that gain-of-function mutant p53 (R175H, R273H, and D281G) promotes AXL expression at both the RNA and protein level44. Thus, we are investigating the roles of p53 loss of function and gain of function to better understand AXL upregulation, although the roles can vary according...