Sperandio Sabina, Tardito Saverio, Surzycki Aleksandra, Latterich Martin, de Belle Ian
Centre de Recherche du CHUL, Department of Molecular Endocrinology and Oncology, Laval University, Quebec, QC Canada.
FEBS Lett. 2009 Jul 7;583(13):2165-70. doi: 10.1016/j.febslet.2009.06.004. Epub 2009 Jun 7.
The TOE1 gene was discovered as a target of the Egr1 transcription factor that participates in cell growth regulation through the upregulation of p21 and a cell cycle delay at the G2/M phase. We report here that TOE1 is able to bind to the p53 tumor suppressor protein, specifically interacting with the C terminal tetramerization domain of p53. We have further characterized this interaction through determination of binding kinetics using nanoporous optical interferometry and demonstrated that this interaction is capable of enhancing the transcriptional activity of p53-dependent gene targets. These results suggest a mechanistic role for TOE1 as a co-regulator of p53.
TOE1基因是作为Egr1转录因子的一个靶点被发现的,Egr1转录因子通过上调p21并使细胞周期在G2/M期延迟来参与细胞生长调控。我们在此报告,TOE1能够与p53肿瘤抑制蛋白结合,特别是与p53的C末端四聚化结构域相互作用。我们通过使用纳米多孔光学干涉测量法测定结合动力学进一步表征了这种相互作用,并证明这种相互作用能够增强p53依赖性基因靶点的转录活性。这些结果表明TOE1作为p53的共调节因子具有机制性作用。