CCT chaperonin complex is required for the biogenesis of functional Plk1
CCT chaperonin complex is required for the biogenesis of functional Plk1
复制标题
DOI：
10.1128/mcb.25.12.4993-5010.2005
复制
发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Erikson, RL
中科院分区：
文献类型：
--
作者：
Liu, XQ;Lin, CY;Erikson, RL
几种不同生物的实验表明，polo样激酶参与有丝分裂和胞质分裂的许多方面。在这里，我们提供的证据表明，Plk1协会与伴侣蛋白含有TCP 1复合物（CCT）在体外和体内。在哺乳动物细胞中通过使用RNA干扰（RNAi）沉默CCT抑制细胞增殖，降低细胞活力，导致细胞周期停滞和4N DNA含量，并导致细胞凋亡。在高度同步化的HeLa细胞中，CCT的耗尽导致细胞周期停滞在G（2），如低有丝分裂指数和Cdc2活性所示。Plk1在同步化良好的细胞中的完全耗尽也导致G2阻滞，这表明错误折叠的Plk1可能是导致CCT耗尽的细胞无法进入有丝分裂的原因。此外，CCT或Plk1的部分缺失导致有丝分裂停滞。最后，CCT耗尽的细胞重新进入细胞周期后，重新引入纯化的组成型活性形式的Plk1，表明Plk1可能是CCT底物。
Experiments from several different organisms have demonstrated that polo-like kinases are involved in many aspects of mitosis and cytokinesis. Here, we provide evidence to show that Plk1 associates with chaperonin-containing TCP1 complex (CCT) both in vitro and in vivo. Silencing of CCT by use of RNA interference (RNAi) in mammalian cells inhibits cell proliferation, decreases cell viability, causes cell cycle arrest with 4N DNA content, and leads to apoptosis. Depletion of CCT in well-synchronized HeLa cells causes cell cycle arrest at G(2), as demonstrated by a low mitotic index and Cdc2 activity. Complete depletion of Plk1 in well-synchronized cells also leads to G2 block, suggesting that misfolded Plk1 might be responsible for the failure of CCT-depleted cells to enter mitosis. Moreover, partial depletion of CCT or Plk1 leads to mitotic arrest. Finally, the CCT-depleted cells reenter the cell cycle upon reintroduction of the purified constitutively active form of Plk1, indicating that Plk1 might be a CCT substrate.