Activation of CTP:phosphocholine cytidylyltransferase α expression during the S phase of the cell cycle is mediated by the transcription factor Sp1

被引:39
作者
Banchio, C
Schang, LM
Vance, DE [1 ]
机构
[1] Univ Alberta, Dept Biochem, Edmonton, AB T6G 2S2, Canada
[2] Univ Alberta, Canadian Inst Hlth, Res Grp Mol & Cell Biol Lipids, Edmonton, AB T6G 2S2, Canada
关键词
D O I
10.1074/jbc.M304810200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:32457 / 32464
页数:8
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