Both p53 loss and reduction of the mitotic kinesin, centromere-associated protein-E, cause low CIN. Combining both genetic insults in the same cell leads to high CIN. Here, we test whether high CIN causes cell death and tumor suppression even in the absence p53.

2024年1月2日 · Here, we study the mutp53 interactome and find that by targeting minichromosome maintenance complex components (MCMs), GOF mutp53 predisposes cells to replication stress and chromosomal instability...

Cell cycle arrest and cell death are two well-studied consequences of p53 activation, but, while being considered critical, they do not fully explain the consequences of p53 loss-of-function phenotypes in cancer. Here, we discuss how mitotic errors alert the p53 network and give an overview of multiple ways that p53 can trigger cell death.

2023年8月15日 · TP53编码的p53蛋白被细胞毒性应激激活，修饰下游基因的转录，主要参与细胞周期调节、凋亡和DNA修复。 大约50%的人类癌症携带TP53突变，TP53也是胃肠道癌症中突变发生率较高的基因之一。 大约30%的TP53突变聚集在DNA结合域（DBD）六个突变热点：R175、G245、R248、R249、R273和R282，表现出功能获得（GOF）特征，获得不属于野生型（wt）p53蛋白的新功能。 此外，TP53突变类型（缺失、插入、颠换和转换）可以反映特定 …

2023年3月1日 · Here, we provide a systematic review of the diverse molecular mechanisms of the p53 signaling pathway and how TP53 mutations impact tumor progression. We also discuss key structural features of...

2024年5月10日 · p53是调节葡萄糖、脂质、氨基酸、核苷酸、铁和氧化还原代谢的重要调节因子（参见）。此外，它还调节自噬，并与AMPK、AKT和mTOR等关键代谢调节因子存在广泛的交互作用。p53的这一功能将其与多种代谢性疾病（包括癌症）联系起来。

2019年8月1日 · The action of p53 in protecting against aneuploidy stems from its activation in cells with numeric chromosomal aberrations (extra or missing chromosomes) . Activation of p53 is triggered in cells with chromosomal aberrations, and thus, p53 mutations are selected in …

2024年3月27日 · 肿瘤蛋白 p53 （TP53） 是编码 p53 的关键抑癌基因，可调节多种下游基因和细胞表型以响应各种胞内外压力应激。 参与多种生物学过程，包括细胞周期停滞、DNA损伤修复、细胞衰老、代谢稳态、细胞凋亡和自噬等。 p53在控制肿瘤细胞命运方面具有新颖和意想不到的功能，近年来基于p53开发了几种有潜力的肿瘤治疗方法，这些方法可能通过对p53的新功能的新见解以及对作用机制和药物递送方式的理解加深而使靶点可成药性增加。 并且，这对p53的深入了解 …

2017年9月8日 · p53 is a sequence-specific DNA binding protein that regulates transcription (reviewed in Laptenko and Prives, 2006). The p53 protein consists of two N-terminal transactivation domains followed by a conserved proline-rich domain, a central DNA binding domain, and a C terminus encoding its nuclear localization signals and an oligomerization ...

2021年1月4日 · Both p53 loss and reduction of the mitotic kinesin, centromere-associated protein-E, cause low CIN. Combining both genetic insults in the same cell leads to high CIN. Here, we test whether high CIN causes cell death and tumor suppression even in the absence p53.