关于 p53 在细胞应对非整倍体中的作用。
On the role of p53 in the cellular response to aneuploidy.
机构信息
Center for Cell Dynamics and Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Center for Cell Dynamics and Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Medical Scientist Training Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Cell Rep. 2021 Mar 23;34(12):108892. doi: 10.1016/j.celrep.2021.108892.
Most solid tumors are aneuploid, and p53 has been implicated as the guardian of the euploid genome. Previous experiments using human cell lines showed that aneuploidy induction leads to p53 accumulation and p21-mediated G1 cell cycle arrest. We find that adherent 2-dimensional (2D) cultures of human immortalized or cancer cell lines activate p53 upon aneuploidy induction, whereas suspension cultures of a human lymphoid cell line undergo a p53-independent cell cycle arrest. Surprisingly, 3D human and mouse organotypic cultures from neural, intestinal, or mammary epithelial tissues do not activate p53 or arrest in G1 following aneuploidy induction. p53-deficient colon organoids have increased aneuploidy and frequent lagging chromosomes and multipolar spindles during mitosis. These data suggest that p53 may not act as a universal surveillance factor restricting the proliferation of aneuploid cells but instead helps directly or indirectly ensure faithful chromosome transmission likely by preventing polyploidization and influencing spindle mechanics.
大多数实体瘤是非整倍体的，p53 被认为是整倍体基因组的守护者。以前使用人细胞系的实验表明，非整倍体诱导导致 p53 积累和 p21 介导的 G1 细胞周期停滞。我们发现，人永生化或癌细胞系的贴壁 2 维（2D）培养物在非整倍体诱导时激活 p53，而人淋巴母细胞系的悬浮培养物则发生 p53 非依赖性细胞周期停滞。令人惊讶的是，来自神经、肠或乳腺上皮组织的 3D 人源和鼠源器官培养物在非整倍体诱导后不会激活 p53 或停滞在 G1 期。p53 缺陷型结肠类器官在有丝分裂过程中具有更高的非整倍体和频繁的滞后染色体和多极纺锤体。这些数据表明，p53 可能不作为限制非整倍体细胞增殖的普遍监测因子起作用，而是通过防止多倍体化和影响纺锤体力学来直接或间接帮助确保染色体的准确传递。
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