有丝分裂灾难中的半胱天冬酶2：非整倍体和四倍体细胞的终结者。
Caspase 2 in mitotic catastrophe: The terminator of aneuploid and tetraploid cells.
作者信息
Vitale Ilio, Manic Gwenola, Castedo Maria, Kroemer Guido
机构信息
Department of Biology, University of Rome "Tor Vergata," Rome, Italy.
Regina Elena National Cancer Institute, Rome, Italy.
出版信息
Mol Cell Oncol. 2017 Mar 10;4(3):e1299274. doi: 10.1080/23723556.2017.1299274. eCollection 2017.
Abstract
Mitotic catastrophe is an oncosuppressive mechanism that targets cells experiencing defective mitoses via the activation of specific cell cycle checkpoints, regulated cell death pathways and/or cell senescence. This prevents the accumulation of karyotypic aberrations, which otherwise may drive oncogenesis and tumor progression. Here, we summarize experimental evidence confirming the role of caspase 2 (CASP2) as the main executor of mitotic catastrophe, and we discuss the signals that activate CASP2 in the presence of mitotic aberrations. In addition, we summarize the main p53-dependent and -independent effector pathways through which CASP2 limits chromosomal instability and non-diploidy, hence mediating robust oncosuppressive functions.
摘要
有丝分裂灾难是一种肿瘤抑制机制，它通过激活特定的细胞周期检查点、调控细胞死亡途径和/或细胞衰老来靶向经历有丝分裂缺陷的细胞。这可防止核型畸变的积累，否则可能会驱动肿瘤发生和肿瘤进展。在这里，我们总结了实验证据，证实半胱天冬酶2（CASP2）作为有丝分裂灾难的主要执行者的作用，并讨论在有丝分裂畸变情况下激活CASP2的信号。此外，我们总结了CASP2限制染色体不稳定性和非二倍体的主要p53依赖性和非依赖性效应途径，从而介导强大的肿瘤抑制功能。
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