VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis.
VRK1 and AURKB form a complex that cross inhibit their kinase activity and the phosphorylation of histone H3 in the progression of mitosis.
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DOI：
10.1007/s00018-018-2746-7
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Lazo PA
中科院分区：
文献类型：
--
作者：
Moura DS;Campillo-Marcos I;Vázquez-Cedeira M;Lazo PA
细胞分裂的调控需要整合与染色质重组有关的信号，并协调其在有丝分裂中的顺序变化。牛痘相关激酶1（VRK 1）和极光B（AURKB）是参与细胞分裂的不同步骤的两种核激酶。我们已经研究了这两种核激酶之间是否存在任何功能联系，这两种核激酶分别在Thr 3和Ser 10中磷酸化组蛋白H3。VRK 1和AURKB能够形成稳定的蛋白质复合物，其仅代表细胞内每种激酶的次要亚群，并且在诺考达唑释放后被检测到。每种激酶都能够抑制另一种激酶的激酶活性，以及抑制它们对组蛋白H3的特异性磷酸化。在两种激酶相互作用的位置，有不同的组蛋白修饰模式，表明有丝分裂期间染色质存在局部差异，因为这些激酶形成的局部复合物及其不对称的细胞内分布。VRK 1的消耗下调识别H3-T3 ph的BIRC 5（生存素）的基因表达，两者都依赖于VRK 1的活性，并且用激酶活性鼠VRK 1恢复，但不用激酶死亡蛋白。H3-Thr 3 ph-生存素复合物是AURB募集所必需的，它们的缺失阻止ACA和AURKB在着丝粒中的定位。有丝分裂末期激酶的交叉抑制可能促进子细胞的形成。VRK 1，AURKB和haspin在有丝分裂的进展中的顺序作用。本文的在线版本（10.1007/s 00018 -018-2746-7）包含补充材料，可供授权用户使用。
Regulation of cell division requires the integration of signals implicated in chromatin reorganization and coordination of its sequential changes in mitosis. Vaccinia-related kinase 1 (VRK1) and Aurora B (AURKB) are two nuclear kinases involved in different steps of cell division. We have studied whether there is any functional connection between these two nuclear kinases, which phosphorylate histone H3 in Thr3 and Ser10, respectively. VRK1 and AURKB are able to form a stable protein complex, which represents only a minor subpopulation of each kinase within the cell and is detected following nocodazole release. Each kinase is able to inhibit the kinase activity of the other kinase, as well as inhibit their specific phosphorylation of histone H3. In locations where the two kinases interact, there is a different pattern of histone modifications, indicating that there is a local difference in chromatin during mitosis because of the local complexes formed by these kinases and their asymmetric intracellular distribution. Depletion of VRK1 downregulates the gene expression of BIRC5 (survivin) that recognizes H3-T3ph, both are dependent on the activity of VRK1, and is recovered with kinase active murine VRK1, but not with a kinase-dead protein. The H3–Thr3ph–survivin complex is required for AURB recruitment, and their loss prevents the localization of ACA and AURKB in centromeres. The cross inhibition of the kinases at the end of mitosis might facilitate the formation of daughter cells. A sequential role for VRK1, AURKB, and haspin in the progression of mitosis is proposed. The online version of this article (10.1007/s00018-018-2746-7) contains supplementary material, which is available to authorized users.
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影响因子：
3.5
作者：
Lopez-Sanchez, Inmaculada;Valbuena, Alberto;Lazo, Pedro A.
通讯作者：
Lazo, Pedro A.
影响因子：
5.3
作者：
Kang, Tae-Hong;Park, Do-Young;Kim, Kyong-Tai
通讯作者：
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DOI：
10.18632/aging.101194
发表时间：
2017-03-10
期刊：
Aging
影响因子：
--
作者：
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通讯作者：
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影响因子：
4
作者：
Kang, Tae-Hong;Park, Do-Young;Kim, Kyong-Tai
通讯作者：
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影响因子：
4.3
作者：
Dai, J;Higgins, JMG
通讯作者：
Higgins, JMG