Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase
Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase
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DOI：
10.1016/j.yexcr.2004.11.027
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发表时间：
2005-04-01
影响因子：
3.7
通讯作者：
Yamaguchi, N
中科院分区：
文献类型：
--
作者：
Nakayama, Y;Yamaguchi, N
CHK酪氨酸激酶使Src家族酪氨酸激酶磷酸化，并抑制其活性。我们最近发现Chk定位于胞核和胞浆，并抑制细胞增殖。为了研究核Chk在细胞增殖中的作用，构建并表达了多种Chk突变体。Chk诱导的动态多分叶状细胞核定位，延长了细胞周期的S时相。Chk的N-末端结构域和它的一部分激酶结构域而不是激酶活性是导致多分叶形成的原因。细胞分选分析显示，S晚期有核多叶细胞浓集。多个分叶状核被层蛋白B1包围，层蛋白B1尤其集中在核的凹陷区。此外，诺康唑或紫杉醇的治疗破坏了细胞核的多分叶。这些结果提示，S期晚期依赖于微管聚合和解聚的核多分叶现象可能参与了Chk诱导的核增殖抑制。(C)2004 Elsevier Inc.保留所有权利。
Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation. (c) 2004 Elsevier Inc. All rights reserved.