Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle.

Role of polyamines at the G1/S boundary and G2/M phase of the cell cycle.
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DOI:
10.1016/j.biocel.2013.02.021
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发表时间:
2013-06
期刊:
The international journal of biochemistry & cell biology
影响因子:
--
通讯作者:
Tomoko Yamashita;K. Nishimura;Ryotaro Saiki;H. Okudaira;M. Tome;Kyohei Higashi;Mizuho Nakamura;Y. Terui;K. Fujiwara;K. Kashiwagi;K. Igarashi
Tomoko Yamashita;K. Nishimura;Ryotaro Saiki;H. Okudaira;M. Tome;Kyohei Higashi;Mizuho Nakamura;Y. Terui;K. Fujiwara;K. Kashiwagi;K. Igarashi
中科院分区:
其他
文献类型:
--
作者:
Tomoko Yamashita;K. Nishimura;Ryotaro Saiki;H. Okudaira;M. Tome;Kyohei Higashi;Mizuho Nakamura;Y. Terui;K. Fujiwara;K. Kashiwagi;K. Igarashi

文献摘要

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多胺在G1/S边界和在G2/M期的细胞周期的作用进行了研究,使用同步化的HeLa细胞处理与胸苷或与胸苷和aphidicolin。在不存在或存在α-二氟甲基鸟氨酸(DFMO)(一种鸟氨酸脱羧酶抑制剂)和乙基乙二醛双(鸟苷酰腙)(EGBG)(一种S-腺苷甲硫氨酸脱羧酶抑制剂)的情况下培养同步化细胞。当DFMO和EGBG处理降低多胺含量时,G1期向S期的转变被延迟。与此同时,p27 Kip 1的表达水平也明显升高,因此对其机制进行了详细的研究。由于p27 Kip 1 mRNA中存在较长的5′-非翻译区(5′-UTR),多胺水平的降低在翻译水平上刺激了p27 Kip 1 mRNA的合成。同样,从G2/M期到G1期的过渡被多胺水平的降低所延迟。与此同时,多核细胞的数量增加了3倍。这与由于肌动蛋白和α-微管蛋白在M期的异常分布而引起的胞质分裂抑制平行。由于多胺与染色体的协会没有观察到免疫荧光显微镜在M期,多胺可能只有一个微小的作用,在M期染色体的结构变化。在一般情况下,多胺在G2/M相的参与小于在G1/S边界。
The role of polyamines at the G1/S boundary and in the G2/M phase of the cell cycle was studied using synchronized HeLa cells treated with thymidine or with thymidine and aphidicolin. Synchronized cells were cultured in the absence or presence of α-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, plus ethylglyoxal bis(guanylhydrazone) (EGBG), an inhibitor of S-adenosylmethionine decarboxylase. When polyamine content was reduced by treatment with DFMO and EGBG, the transition from G1to S phase was delayed. In parallel, the level of p27Kip1was greatly increased, so its mechanism was studied in detail. Synthesis of p27Kip1was stimulated at the level of translation by a decrease in polyamine levels, because of the existence of long 5′-untranslated region (5′-UTR) in p27Kip1mRNA. Similarly, the transition from the G2/M to the G1phase was delayed by a reduction in polyamine levels. In parallel, the number of multinucleate cells increased by 3-fold. This was parallel with the inhibition of cytokinesis due to an unusual distribution of actin and α-tubulin at the M phase. Since an association of polyamines with chromosomes was not observed by immunofluorescence microscopy at the M phase, polyamines may have only a minor role in structural changes of chromosomes at the M phase. In general, the involvement of polyamines at the G2/M phase was smaller than that at the G1/S boundary.