p53 is a sequence-specific transcription factor, and proper regulation of p53 transcriptional activity is critical for orchestrating different tumor-suppressive mechanisms. p32 is a multifunctional protein which interacts with a large number of viral proteins and transcription factors. Here, we investigate the effect of p32 on p53 transactivation and identify a novel mechanism by which p32 alters the functional characteristics of p53. Specifically, p32 attenuates p53-dependent transcription through impairment of p53 binding to its response elements on target genes. Upon p32 expression, p53 levels bound at target genes are decreased, and p53 target genes are inactivated, strongly indicating that p32 restricts p53 occupancy and function at target genes. The primary mechanism contributing to the observed action of p32 is the ability of p32 to interact with the p53 tetramerization domain and to block p53 tetramerization, which in turn enhances nuclear export and degradation of p53, leading to defective p53 transactivation. Collectively, these data establish p32 as a negative regulator of p53 function and suggest the therapeutic potential of targeting p32 for cancer treatment.

中文翻译：

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p32 是 p53 四聚化和反式激活的负调节因子。

p53 是一种序列特异性转录因子，p53 转录活性的正确调节对于协调不同的肿瘤抑制机制至关重要。p32 是一种多功能蛋白，可与大量病毒蛋白和转录因子相互作用。在这里，我们研究了 p32 对 p53 反式激活的影响，并确定了 p32 改变 p53 功能特征的新机制。具体来说，p32 通过损害 p53 与其靶基因上的反应元件的结合来减弱 p53 依赖性转录。p32 表达后，与靶基因结合的 p53 水平降低，p53 靶基因失活，强烈表明 p32 限制 p53 在靶基因上的占据和功能。促成观察到的 p32 作用的主要机制是 p32 与 p53 四聚化结构域相互作用并阻断 p53 四聚化的能力，这反过来又增强了 p53 的核输出和降解，导致 p53 反式激活缺陷。总的来说，这些数据确立了 p32 作为 p53 功能的负调节因子，并表明以 p32 为靶点进行癌症治疗的治疗潜力。