Vanadate triggers the transition from chromosome condensation to decondensation in a mitotic mutant (tsTM13) - Inactivation of p34(cdc2)/H1 kinase and dephosphorylation of mitosis-specific histone H3
Vanadate triggers the transition from chromosome condensation to decondensation in a mitotic mutant (tsTM13) - Inactivation of p34(cdc2)/H1 kinase and dephosphorylation of mitosis-specific histone H3
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DOI：
10.1111/j.1432-1033.1996.00923.x
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发表时间：
1996-11-01
期刊：
影响因子：
--
通讯作者：
Tsuji, H
中科院分区：
文献类型：
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作者：
Ajiro, K;Yasuda, H;Tsuji, H
在非允许温度下（39摄氏度），染色体在有丝分裂后期被抑制的温度敏感细胞突变体（tsTM13）中保持凝聚。组蛋白H1激酶活性的高度增加，组蛋白H1的过度磷酸化，以及有丝分裂特异性组蛋白H3的磷酸化，即使在末期也是如此。本研究发现，酪氨酸磷酸酶抑制剂钒酸盐可使tsTM13细胞染色体去浓缩缺陷部分正常化，诱导染色体去浓缩，形成多核细胞。在钒酸盐存在下，H1激酶活性下降到接近正常水平，酪氨酸残基磷酸化的p34（cdc2）蛋白的失活形式的数量增加。H1和H3也被广泛地去磷酸化，后者与染色体去浓缩密切相关。结果表明：(a)突变体的遗传缺陷可能与M期晚期p34(cdc2)/H1激酶活性的控制机制有关，而不是磷酸酶；(b)钒酸盐对突变体缺陷的正常化是由H1激酶失活引起的；(c)有丝分裂晚期特异性事件（p34(cdc2)/H1激酶失活）。有丝分裂特异性组蛋白H1和H3的去磷酸化与染色体去浓缩密切相关。
At the nonpermissive temperature (39 degrees C), chromosomes remain condensed in a temperature-sensitive cell mutant (tsTM13) arrested in the late stage of mitosis. Highly increased activity of histone H1 kinase, hyperphosphorylation of histone H1, and mitosis-specific histone H3 phosphorylation are maintained, even in telophase. In the present study, the defect of chromosome decondensation in tsTM13 cells was found to be partially normalized by a tyrosine phosphatase inhibitor, vanadate, with induction of chromosome decondensation and the formation of multinucleated cells. In the presence of vanadate, the H1 kinase activity dropped to near normal levels and the amount of the inactive form of p34(cdc2) protein phosphorylated at a tyrosine residue was increased. H1 and H3 were also extensively de- phosphorylated, the latter being tightly associated with chromosome decondensation. Serine/threonine-protein phosphatase in late mitosis of the mutant works normally at 39 degrees C. The results indicate that (a) the genetic defect in the mutant may be involved in the control mechanism of the p34(cdc2)/H1 kinase activity in the late M phase rather than the phosphatase, (b) normalization of the defect of the mutant by vanadate results from inactivation of H1 kinase, and (c) late mitosis-specific events (p34(cdc2)/H1 kinase inactivation, mitosis-specific dephosphorylation of histone H1 and H3) are closely operating with chromosome decondensation.