The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth
The yeast lipin Smp2 couples phospholipid biosynthesis to nuclear membrane growth
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DOI：
10.1038/sj.emboj.7600672
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发表时间：
2005-06-01
期刊：
影响因子：
11.4
通讯作者：
Siniossoglou, S
中科院分区：
文献类型：
--
作者：
Santos-Rosa, H;Leung, J;Siniossoglou, S
在细胞周期的不同阶段和细胞分化过程中，核膜的重构对于核结构的动态变化是必不可少的。调节核膜生物发生的分子机制尚不清楚。在这里，我们表明，Smp 2，酵母同系物的哺乳动物脂蛋白，是一个关键的调节核膜生长在细胞周期。Smp 2被Cdc 28/Cdk 1磷酸化并被由Nem 1和Spo 7组成的核/内质网（ER）膜定位的CPD磷酸酶复合物去磷酸化。SMP 2或其去磷酸化形式的缺失导致参与脂质生物合成的关键酶的转录上调，同时细胞核大量扩增。相反，Smp 2的组成性去磷酸化抑制细胞分裂。我们发现，Smp 2协会与磷脂生物合成酶的启动子在Nem 1-Spo 7依赖的方式。我们的数据表明，Smp 2是一个关键因素，在协调磷脂的生物合成在细胞周期的核/ER膜与核生长。
Remodelling of the nuclear membrane is essential for the dynamic changes of nuclear architecture at different stages of the cell cycle and during cell differentiation. The molecular mechanism underlying the regulation of nuclear membrane biogenesis is not known. Here we show that Smp2, the yeast homologue of mammalian lipin, is a key regulator of nuclear membrane growth during the cell cycle. Smp2 is phosphorylated by Cdc28/ Cdk1 and dephosphorylated by a nuclear/endoplasmic reticulum (ER) membrane - localized CPD phosphatase complex consisting of Nem1 and Spo7. Loss of either SMP2 or its dephosphorylated form causes transcriptional upregulation of key enzymes involved in lipid biosynthesis concurrent with a massive expansion of the nucleus. Conversely, constitutive dephosphorylation of Smp2 inhibits cell division. We show that Smp2 associates with the promoters of phospholipid biosynthetic enzymes in a Nem1 - Spo7-dependent manner. Our data suggest that Smp2 is a critical factor in coordinating phospholipid biosynthesis at the nuclear/ER membrane with nuclear growth during the cell cycle.