Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration.

Actin-myosin-based contraction is responsible for apoptotic nuclear disintegration.
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基于肌动蛋白肌球蛋白的收缩负责凋亡的核崩解。

DOI:
10.1083/jcb.200409049
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发表时间:
2005-01-17
影响因子:
7.8
通讯作者:
Olson, MF
Olson, MF
中科院分区:
生物学1区
文献类型:
--
作者:
Croft, DR;Coleman, ML;Li, SX;Robertson, D;Sullivan, T;Stewart, CL;Olson, MF

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细胞凋亡执行阶段的膜起泡是由半胱天冬酶介导的ROCK I裂解和激活引起的。在这里,我们表明,ROCK活性,肌球蛋白轻链(MLC)磷酸化,MLC ATP酶活性,和一个完整的肌动蛋白细胞骨架,但不是微管细胞骨架,需要在细胞凋亡过程中破坏核的完整性。ROCK或MLC ATP酶活性的抑制可保护凋亡细胞核的完整性,但不影响半胱天冬酶介导的核蛋白(如核纤层蛋白A、B1或C)降解。ROCK I的条件性激活足以撕裂核核纤层蛋白A/C空成纤维细胞,但不是在野生型成纤维细胞。因此,细胞凋亡的核解体需要肌动蛋白-肌球蛋白收缩力和核纤层蛋白的蛋白水解,使细胞凋亡类似于,但不同于,有丝分裂,其中核解体的结果从微管为基础的力量和核纤层蛋白磷酸化和解聚。
Membrane blebbing during the apoptotic execution phase results from caspase-mediated cleavage and activation of ROCK I. Here, we show that ROCK activity, myosin light chain (MLC) phosphorylation, MLC ATPase activity, and an intact actin cytoskeleton, but not microtubular cytoskeleton, are required for disruption of nuclear integrity during apoptosis. Inhibition of ROCK or MLC ATPase activity, which protect apoptotic nuclear integrity, does not affect caspase-mediated degradation of nuclear proteins such as lamins A, B1, or C. The conditional activation of ROCK I was sufficient to tear apart nuclei in lamin A/C null fibroblasts, but not in wild-type fibroblasts. Thus, apoptotic nuclear disintegration requires actin-myosin contractile force and lamin proteolysis, making apoptosis analogous to, but distinct from, mitosis where nuclear disintegration results from microtubule-based forces and from lamin phosphorylation and depolymerization.
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