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有丝分裂与细胞凋亡:平衡如何设定?

Mitosis and apoptosis: how is the balance set?

机构信息

Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, UK.

出版信息

Curr Opin Cell Biol. 2013 Dec;25(6):780-5. doi: 10.1016/j.ceb.2013.07.003. Epub 2013 Jul 23.

Abstract

Anti-mitotic agents are used extensively during cancer chemotherapy. These agents target microtubules and thus block mitotic progression by activating the spindle assembly checkpoint. Following a prolonged mitotic arrest, cells either die in mitosis via apoptosis, or exit mitosis without dividing and survive, a process known as slippage. What dictates the balance between these two fates is unclear, but recent advances highlight the importance of the pro-survival Bcl2 family, with Mcl1 degradation emerging as a key determinant of mitotic cell fate. Here we review these advances, with a view towards identifying how the balance between apoptosis and slippage can be tipped in favour of death. This in turn may open up new opportunities to sensitize cancer cells to anti-mitotic agents.

摘要

抗有丝分裂剂在癌症化疗中被广泛应用。这些药物靶向微管,通过激活纺锤体组装检查点来阻止有丝分裂的进行。在长时间的有丝分裂阻滞后,细胞要么通过凋亡在有丝分裂中死亡,要么不分裂就退出有丝分裂并存活下来,这个过程被称为滑走。决定这两种命运之间平衡的因素尚不清楚,但最近的进展强调了生存 Bcl2 家族的重要性,Mcl1 的降解成为有丝分裂细胞命运的关键决定因素。在这里,我们回顾这些进展,以期确定如何使凋亡和滑走之间的平衡有利于死亡。这反过来又可能为使癌细胞对抗有丝分裂剂敏感开辟新的机会。

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