The p53-caspase-2 axis in the cell cycle and DNA damage response.
The p53-caspase-2 axis in the cell cycle and DNA damage response.
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DOI：
10.1038/s12276-021-00590-2
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发表时间：
2021-04
影响因子：
12.8
通讯作者：
Kumar S
中科院分区：
文献类型：
--
作者：
Lim Y;Dorstyn L;Kumar S
Caspase-2是近30年前发现的。它是CED-3最早的两个哺乳动物同源物之一，另一个是白细胞介素1β转换酶(ICE/Caspase-1)。尽管caspase-2与CED-3、Fly和哺乳动物的同源基因(分别为DRONC和caspase-9)有很高的相似性，但caspase-2在细胞凋亡中的作用仍然是个谜。最近的一些研究表明，caspase-2在细胞应激和DNA损伤中调节P53以防止受损或异常细胞的增殖和积聚中发挥重要作用。在这里，我们回顾了这些最新的观察结果及其在caspase-2介导的细胞死亡、衰老和肿瘤抑制中的意义。在DNA损伤或有丝分裂应激等条件下，caspase-2酶在调节抑癌蛋白P53的稳定性方面起着至关重要的作用。半胱氨酸天冬氨酸氨基转移酶在细胞内稳态、炎症和程序性细胞死亡中发挥多种作用。澳大利亚阿德莱德大学癌症生物学中心的Sharad Kumar和他的同事们回顾了目前对caspase-2及其与p53的联系的理解。Caspase-2缺乏导致P53信号缺陷，这表明这两个分子之间存在调控联系。最近的研究表明，在DNA损伤或胞质分裂失败后，caspase-2裂解MDM2，p53泛素连接酶，以稳定p53。这可以防止受损细胞的增殖、非整倍体和潜在的癌前细胞的积累。在几种模型中，caspase-2水平降低与癌症进展加速有关。P53的调节功能可能解释了caspase-2的这种肿瘤抑制活性。
Caspase-2 was discovered almost three decades ago. It was one of the first two mammalian homologs of CED-3, the other being interleukin 1β-converting enzyme (ICE/caspase-1). Despite high similarity with CED-3 and its fly and mammalian counterparts (DRONC and caspase-9, respectively), the function of caspase-2 in apoptosis has remained enigmatic. A number of recent studies suggest that caspase-2 plays an important role in the regulation of p53 in response to cellular stress and DNA damage to prevent the proliferation and accumulation of damaged or aberrant cells. Here, we review these recent observations and their implications in caspase-2-mediated cellular death, senescence, and tumor suppression. Under conditions such as DNA damage or mitotic stress, the enzyme caspase-2 plays a vital role in regulating the stability of p53, a tumor suppressor protein. Caspases play multiple roles in cellular homeostasis, inflammation and programmed cell death. Sharad Kumar and colleagues at the Centre for Cancer Biology, UniSA in Adelaide, Australia, review current understanding of caspase-2 and its links with p53. Caspase-2 deficiency leads to defective p53 signaling, suggesting a regulatory link between the two molecules. Recent studies suggest that following DNA damage or cytokinesis failure caspase-2 cleaves MDM2, the p53 ubiquitin ligase, to stabilize p53. This prevents the proliferation of damaged cells, aneuploidy and accumulation of potentially premalignant cells. Reduced caspase-2 levels are associated with enhanced cancer progression in several models. The p53 regulatory function may explains this tumor suppressive activity of caspase-2.
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影响因子：
32.4
作者：
Bronner DN;Abuaita BH;Chen X;Fitzgerald KA;Nuñez G;He Y;Yin XM;O'Riordan MX
通讯作者：
O'Riordan MX
影响因子：
4.8
作者：
Guo, Y;Srinivasula, SM;Alnemri, ES
通讯作者：
Alnemri, ES
影响因子：
64.8
作者：
Duan, H;Dixit, VM
通讯作者：
Dixit, VM
影响因子：
5.5
作者：
Brown-Suedel AN;Bouchier-Hayes L
通讯作者：
Bouchier-Hayes L
影响因子：
10.5
作者：
Fava, Luca L.;Schuler, Fabian;Villunger, Andreas
通讯作者：
Villunger, Andreas