The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53.
The microtubule cytoskeleton is required for a G2 cell cycle delay in cancer cells lacking stathmin and p53.
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DOI：
10.1002/cm.21024
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发表时间：
2012-05
期刊：
影响因子：
2.9
通讯作者：
Cassimeris, Lynne
中科院分区：
文献类型：
--
作者：
Carney, Bruce K.;Silva, Victoria Caruso;Cassimeris, Lynne
在几个癌细胞系中，耗尽微管破坏稳定的蛋白stathmin/oncotein 18会导致G2期细胞周期延迟和细胞凋亡。这些表型只有在与低水平的P53协同作用时才能观察到，但stthmin耗尽激活的延迟细胞周期的途径(S)尚不清楚。我们发现，通过乙酰化α-微管蛋白水平和中心体微管形核率的测量，Stathmin的耗竭与P53的丢失协同作用导致了更大的微管稳定性。诺可达唑或长春花碱诱导的微管解聚消除了他汀类药物耗竭引起的G2延迟，通过几种标志物(具有抑制磷酸化的TPX2、CDK1)染色阳性的细胞百分比来衡量，表明微管需要延长G2。活细胞成像显示，Stathmin耗尽增加了G2中的时间，但对有丝分裂的持续时间没有影响，表明较长的间期持续时间不仅仅是先前缓慢的有丝分裂的结果。相比之下，用紫杉醇(8 NM)稳定微管可以在不延长间期持续时间的情况下减缓有丝分裂，这表明仅增加微管的稳定性不足以延迟G2期的细胞。
In several cancer cell lines, depleting the microtubule-destabilizing protein stathmin/oncoprotein18 leads to a G2 cell cycle delay and apoptosis. These phenotypes are observed only in synergy with low levels of p53, but the pathway(s) activated by stathmin depletion to delay the cell cycle are unknown. We found that stathmin depletion caused greater microtubule stability in synergy with loss of p53, measured by the levels of acetylated α-tubulin and the rate of centrosomal microtubule nucleation. Nocodazole or vinblastine-induced microtubule depolymerization abrogated the stathmin-depletion induced G2 delay, measured by the percentage of cells staining positive for several markers (TPX2, CDK1 with inhibitory phosphorylation), indicating that microtubules are required to lengthen G2. Live cell imaging showed that stathmin depletion increased time in G2 without an impact on the duration of mitosis, indicating that the longer interphase duration is not simply a consequence of a previous slowed mitosis. In contrast, stabilization of microtubules with paclitaxel (8 nM) slowed mitosis without lengthening the duration of interphase, demonstrating that increased microtubule stability alone is not sufficient to delay cells in G2.
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