Sp-1 binds promoter elements that are regulated by retinoblastoma and regulate CTP:: Phosphocholine cytidylyltransferase-α transcription

被引:17
作者
Banchio, Claudia [1 ]
Lingrell, Susanne
Vance, Dennis E.
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
[3] Univ Nacl Rosario, Fac Ciencias Bioquim & Farmaceut, Dept Ciencias Biol,Biol Div, Area Biol,Consejo Nacl Invest Cient & Tecn,Inst M, RA-2002 Rosario, Argentina
关键词
D O I
10.1074/jbc.M700527200
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
The retinoblastoma (Rb) protein is implicated in transcriptional regulation of at least five cellular genes. Co-transfection of Rb and truncated promoter constructs has defined a discrete element (retinoblastoma control element (RCE)) within the promoters of each of these genes as being necessary for Rb-mediated transcriptional control. In the present report we demonstrate that two RCEs identified within the CTP: phosphocholine cytidylyltransferase-alpha (CT alpha) proximal promoter are essential to promote transcription. Mutations that abolished each RCE markedly decreased CT alpha transcription. Co-transfection of Rb and truncated promoter constructs demonstrated that Rb regulates CT alpha expression by different mechanisms depending on the phase of the cell cycle. The regulation of CT alpha expression by Rb required both the Sp1 and the RCEs. Maximal expression occurred when both Rb and Sp1 were overexpressed. Moreover, RCEs were required for Rb association with the DNA. This regulatory mechanism alters CT alpha activity and thereafter changes PC availability and cell physiology. This is the first report demonstrating not only that surrounding Sp1 binding sites alter regulation mediated by Rb, but also that the expression of a gene involved in PC biosynthesis shares a common regulatory pathway with genes responsible for cell growth and differentiation.
引用
收藏
页码:14827 / 14835
页数:9
相关论文
共 45 条
[1]   A RAPID MICROPREPARATION TECHNIQUE FOR EXTRACTION OF DNA-BINDING PROTEINS FROM LIMITING NUMBERS OF MAMMALIAN-CELLS [J].
ANDREWS, NC ;
FALLER, DV .
NUCLEIC ACIDS RESEARCH, 1991, 19 (09) :2499-2499
[2]   Transcriptional activation of the murine CTP:phosphocholine cytidylyltransferase gene (Ctpct):: combined action of upstream stimulatory and inhibitory cis-acting elements [J].
Bakovic, M ;
Waite, K ;
Tang, W ;
Tabas, I ;
Vance, DE .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1999, 1438 (01) :147-165
[3]  
Bakovic M, 2000, J LIPID RES, V41, P583
[4]   Phosphorylation of Sp1 by cyclin-dependent kinase 2 modulates the role of Sp1 in CTP:phosphocholine cytidylyltransferase α regulation during the S phase of the cell cycle [J].
Banchio, C ;
Schang, LM ;
Vance, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (38) :40220-40226
[5]   Role of histone deacetylase in the expression of CTP:Phosphocholine cytidylyltransferase α [J].
Banchio, C ;
Lingrell, S ;
Vance, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (15) :10010-10015
[6]   Activation of CTP:phosphocholine cytidylyltransferase α expression during the S phase of the cell cycle is mediated by the transcription factor Sp1 [J].
Banchio, C ;
Schang, LM ;
Vance, DE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (34) :32457-32464
[7]   THE RETINOBLASTOMA PROTEIN AND THE REGULATION OF CELL CYCLING [J].
COBRINIK, D ;
DOWDY, SF ;
HINDS, PW ;
MITTNACHT, S ;
WEINBERG, RA .
TRENDS IN BIOCHEMICAL SCIENCES, 1992, 17 (08) :312-315
[8]   How cytidylyltransferase uses an amphipathic helix to sense membrane phospholipid composition [J].
Cornell, RB .
BIOCHEMICAL SOCIETY TRANSACTIONS, 1998, 26 (03) :539-544
[9]   ANALYSIS OF SP1 INVIVO REVEALS MULTIPLE TRANSCRIPTIONAL DOMAINS, INCLUDING A NOVEL GLUTAMINE-RICH ACTIVATION MOTIF [J].
COUREY, AJ ;
TJIAN, R .
CELL, 1988, 55 (05) :887-898
[10]   GEOMETRICAL PROPERTIES OF MASLOV INDEXES IN THE SEMICLASSICAL TRACE FORMULA FOR THE DENSITY OF STATES [J].
CREAGH, SC ;
ROBBINS, JM ;
LITTLEJOHN, RG .
PHYSICAL REVIEW A, 1990, 42 (04) :1907-1922