Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells
Inositol lipids are regulated during cell cycle progression in the nuclei of murine erythroleukaemia cells
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DOI：
10.1042/0264-6021:3570905
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发表时间：
2001-08-01
影响因子：
4.1
通讯作者：
Divecha, N
中科院分区：
文献类型：
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作者：
Clarke, JH;Letcher, AJ;Divecha, N
以前的数据表明存在离散池肌醇脂质，这是一个核磷酸肌醇（PI）循环的组成部分。然而，尚不清楚这些池的内容物是否在细胞增殖期间受到调节。在本研究中，我们证明了核PI周期的三个重要组成部分的质量水平在细胞周期中进行调节。随着同步化细胞进入S期，观察到放射性标记掺入PtdIns（4，5）P-2中显著增加。这与这种脂质的核质量水平的任何显著变化不一致，表明这种分子的周转率增加。PtdIns 4P是I型PtdInsP激酶（PIPkins）产生PtdIns（4，5）P-2的主要底物，其水平在细胞周期期间受到调节，并表明这两种脂质之间的复杂关系。由II型PIPkin磷酸化的PtdIns（4，5）P-2的替代底物PtdIns 5 P以比PtdIns 4P小得多的量存在于细胞核中，因此不太可能显著促进PtdIns（4，5）P-2周转。然而，当小鼠红白血病细胞处于G（1）时，观察到核PtdIns 5 P质量大幅增加，这可能代表了具有特定信号作用的核肌醇脂质的潜在库。提取的脂质组分的分析表明，在这些细胞核中没有任何PtdIns 3 P。
Previous data suggest the existence of discrete pools of inositol lipids, which are components of a nuclear phosphoinositide (PI) cycle. However, it is not known whether the contents of these pools are regulated during cell proliferation. In the present study we demonstrate that the mass levels of three important constituents of the nuclear PI cycle are regulated during the cell cycle. Radioactive label incorporation into PtdIns(4,5)P-2 was seen to increase dramatically as synchronized cells entered S-phase. This did not coincide with any significant changes in the nuclear mass levels of this lipid, suggesting that the rate of turnover of this molecule was increased. Levels of PtdIns4P, the major substrate for PtdIns(4,5)P-2 production by Type I PtdInsP kinases (PIPkins), were regulated during the cell cycle and indicated a complex relationship between these two lipids. An alternative substrate for PtdIns(4,5)P-2, PtdIns5P, phosphorylated by Type II PIPkins, was present in nuclei at much smaller amounts than the PtdIns4P, and thus is unlikely to contribute significantly to PtdIns(4,5)P-2 turnover. However, a large increase in nuclear PtdIns5P mass was observed when murine erythroleukaemia cells are in G(1), and this could represent a potential pool of nuclear inositol lipid that has a specific signalling role. Analysis of extracted lipid fractions indicated the absence of any PtdIns3P in these nuclei.