Guo X W, Th'ng J P, Swank R A, Anderson H J, Tudan C, Bradbury E M, Roberge M
Department of Biological Chemistry, University of California, Davis 95616.
EMBO J. 1995 Mar 1;14(5):976-85. doi: 10.1002/j.1460-2075.1995.tb07078.x.
Chromosome condensation at mitosis correlates with the activation of p34cdc2 kinase, the hyperphosphorylation of histone H1 and the phosphorylation of histone H3. Chromosome condensation can also be induced by treating interphase cells with the protein phosphatase 1 and 2A inhibitors okadaic acid and fostriecin. Mouse mammary tumour FT210 cells grow normally at 32 degrees C, but at 39 degrees C they lose p34cdc2 kinase activity and arrest in G2 because of a temperature-sensitive lesion in the cdc2 gene. The treatment of these G2-arrested FT210 cells with fostriecin or okadaic acid resulted in full chromosome condensation in the absence of p34cdc2 kinase activity or histone H1 hyperphosphorylation. However, phosphorylation of histones H2A and H3 was strongly stimulated, partly through inhibition of histone H2A and H3 phosphatases, and cyclins A and B were degraded. The cells were unable to complete mitosis and divide. In the presence of the protein kinase inhibitor starosporine, the addition of fostriecin did not induce histone phosphorylation and chromosome condensation. The results show that chromosome condensation can take place without either the histone H1 hyperphosphorylation or the p34cdc2 kinase activity normally associated with mitosis, although it requires a staurosporine-sensitive protein kinase activity. The results further suggest that protein phosphatases 1 and 2A may be important in regulating chromosome condensation by restricting the level of histone phosphorylation during interphase, thereby preventing premature chromosome condensation.
有丝分裂时的染色体凝聚与p34cdc2激酶的激活、组蛋白H1的过度磷酸化以及组蛋白H3的磷酸化相关。用蛋白磷酸酶1和2A抑制剂冈田酸和福司曲星处理间期细胞也可诱导染色体凝聚。小鼠乳腺肿瘤FT210细胞在32℃时正常生长，但在39℃时它们失去p34cdc2激酶活性并因cdc2基因中的温度敏感损伤而停滞在G2期。用福司曲星或冈田酸处理这些停滞在G2期的FT210细胞，在没有p34cdc2激酶活性或组蛋白H1过度磷酸化的情况下导致了完全的染色体凝聚。然而，组蛋白H2A和H3的磷酸化受到强烈刺激，部分是通过抑制组蛋白H2A和H3磷酸酶实现的，并且细胞周期蛋白A和B被降解。细胞无法完成有丝分裂并分裂。在蛋白激酶抑制剂星形孢菌素存在的情况下，添加福司曲星不会诱导组蛋白磷酸化和染色体凝聚。结果表明，染色体凝聚可以在没有通常与有丝分裂相关的组蛋白H1过度磷酸化或p34cdc2激酶活性的情况下发生，尽管它需要一种对星形孢菌素敏感的蛋白激酶活性。结果进一步表明，蛋白磷酸酶1和2A可能通过在间期限制组蛋白磷酸化水平来调节染色体凝聚，从而防止过早的染色体凝聚。
