The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment
The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment
复制标题
DOI：
10.1101/gad.1267105
复制
发表时间：
2005-02-15
影响因子：
10.5
通讯作者：
Higgins, JMG
中科院分区：
文献类型：
--
作者：
Dai, J;Sultan, S;Higgins, JMG
组蛋白中保守的N末端尾部残基的翻译后修饰调节染色体活性的许多方面。组蛋白H3的Thr 3是高度保守的，但其磷酸化的意义尚不清楚，相应的激酶的身份未知。哺乳动物细胞中磷酸化特异性抗体的免疫染色揭示了有丝分裂前期H3 Thr 3的磷酸化和后期的去磷酸化。此外，我们发现，haspin，一个独特的组中存在于不同的真核生物的蛋白激酶的成员，磷酸化H3在Thr 3在体外。重要的是，通过RNA干扰去除haspin揭示了这种激酶是有丝分裂细胞中H3 Thr 3磷酸化所必需的。除了与染色体结合外，在有丝分裂过程中，haspin还存在于中心体和纺锤体中。Haspin RNA干扰导致中期染色体的错位，过表达延迟了早期有丝分裂的进程。这项工作揭示了一个新的激酶参与组成的组蛋白代码，并增加了haspin选择组的激酶，整合在有丝分裂和减数分裂期间的染色体和纺锤体功能的调节。
Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.