Activation of CTP:phosphocholine cytidylyltransferase α expression during the S phase of the cell cycle is mediated by the transcription factor Sp1
Activation of CTP:phosphocholine cytidylyltransferase α expression during the S phase of the cell cycle is mediated by the transcription factor Sp1
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DOI：
10.1074/jbc.m304810200
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发表时间：
2003-08-22
影响因子：
4.8
通讯作者：
Vance, DE
中科院分区：
文献类型：
--
作者：
Banchio, C;Schang, LM;Vance, DE
细胞分裂过程中的一个重要步骤是诱导磷脂酰胆碱的生物合成。在该途径中，CTP：磷酸胆碱胞苷酰转移酶α（CTalpha）起着重要的调节作用。先前的研究（Golfman，L.美国，Bakovic，M.，和万斯，D. E.（2001）J.Biol.Chem.276，43688-43692）证明，在细胞有丝分裂的准备过程中，CT α mRNA在S期积累。我们现在证明，转录因子Sp1的近端启动子CTalpha的结合增加是负责在S期增加转录。存在于位置-67/-62的Sp1结合元件对于激活是必需的，并且位置-31/-9的Sp1位点对于增强转录是必需的。通过RNA干扰抑制Sp1表达可消除CTalpha表达的增强。免疫沉淀研究表明，Sp1与细胞周期蛋白E，细胞周期蛋白A，细胞周期蛋白依赖性激酶2在S期相互作用。我们的结论是，Sp1结合到CT α近端启动子是必要的，以增强转录在S期。这是第一次阐明了一种机制，通过这种机制，磷脂生物合成中的一种关键酶的表达在细胞周期中受到调节。
An essential step during cell division is induction of phosphatidylcholine biosynthesis. In this pathway, CTP: phosphocholine cytidylyltransferase alpha (CTalpha) plays an important regulatory role. Previous studies (Golfman, L. S., Bakovic, M., and Vance, D. E. (2001) J. Biol. Chem. 276, 43688-43692) demonstrated that CTalpha mRNA accumulates during S phase in preparation for cellular mitosis. We now demonstrate that increased binding of the transcription factor Sp1 to the proximal promoter of CTalpha is responsible for increased transcription during the S phase. The Sp1 binding element present in position -67/-62 is essential for activation, and the Sp1 site in position -31/-9 is required to enhance transcription. Inhibition of Sp1 expression by RNA interference abolished the enhanced expression of CTalpha. Immunoprecipitation studies demonstrated that Sp1 interacts with cyclin E, cyclin A, and cyclin-dependent kinase 2 during the S phase. We conclude that Sp1 binding to the CTalpha proximal promoter is necessary to enhance transcription during the S phase. This is the first elucidation of a mechanism by which expression of a key enzyme in phospholipid biosynthesis is regulated during the cell cycle.