Insulin-responsive nuclear proteins facilitate Sp1 interactions with the insulin-like growth factor-I gene

被引:16
作者
Kaytor, EN [1 ]
Zhu, JL [1 ]
Pao, CI [1 ]
Phillips, LS [1 ]
机构
[1] Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA 30322 USA
关键词
D O I
10.1074/jbc.M104035200
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 diabetes-induced decrease in insulin-like growth factor-I transcription appears to be mediated by footprint region V in exon 1. Since region V contains both an Sp1 site and an AT-rich element that recognizes an insulin-responsive binding protein (IRBP), we tested the hypothesis that Sp1 interactions are facilitated by an IRBP. Binding of nuclear extracts to region V probes was reduced by mutational or chemical interference with the AT-rich element. Blocking the AT site also reduced interactions of Sp1 with region V in vitro and blunted transactivation of region V reporter constructs by Sp1 in vivo. Sp1 binding was enhanced by small quantities of hepatic nuclear extracts, but enhancement was reduced by the AT mutation and abolished by a 5-base pair insertion between the AT-rich and GC-rich sites, and transactivation by Sp1 in vivo was diminished by inserting bases between the AT-rich and GC-rich elements. However, treating cells with insulin increased the ability of nuclear extracts to enhance Sp1 binding. These findings indicate that the presence of the AT-rich element is essential for the actions of Sp1 in vitro and in vivo, and the combination of both spacing requirements and insulin responsiveness suggests that IRBP may interact directly with Sp1.
引用
收藏
页码:36896 / 36901
页数:6
相关论文
共 38 条
[1]   TRANSCRIPTION INITIATION IN THE 2 LEADER EXONS OF THE RAT IGF-I GENE OCCURS FROM DISPERSE VERSUS LOCALIZED SITES [J].
ADAMO, ML ;
BENHUR, H ;
LEROITH, D ;
ROBERTS, CT .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 176 (02) :887-893
[2]   Casein kinase II-mediated phosphorylation of the C terminus of spl decreases its DNA binding activity [J].
Armstrong, SA ;
Barry, DA ;
Leggett, RW ;
Mueller, CR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (21) :13489-13495
[3]   STEROL REGULATION OF FATTY-ACID SYNTHASE PROMOTER - COORDINATE FEEDBACK-REGULATION OF 2 MAJOR LIPID PATHWAYS [J].
BENNETT, MK ;
LOPEZ, JM ;
SANCHEZ, HB ;
OSBORNE, TF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1995, 270 (43) :25578-25583
[4]  
BLUNDELL TL, 1983, FED PROC, V42, P2592
[5]   PURIFICATION AND BIOCHEMICAL-CHARACTERIZATION OF THE PROMOTER-SPECIFIC TRANSCRIPTION FACTOR, SPL [J].
BRIGGS, MR ;
KADONAGA, JT ;
BELL, SP ;
TJIAN, R .
SCIENCE, 1986, 234 (4772) :47-52
[6]   Efficient TGF-β induction of the Smad7 gene requires cooperation between AP-1, Sp1, and Smad proteins on the mouse Smad7 promoter [J].
Brodin, G ;
Åhgren, A ;
ten Dijke, P ;
Heldin, CH ;
Heuchel, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (37) :29023-29030
[7]  
Brown MA, 1999, J ANIM SCI, V77, P25
[8]   The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor [J].
Brown, MS ;
Goldstein, JL .
CELL, 1997, 89 (03) :331-340
[9]   Functional interaction between c-Jun and promoter factor Sp1 in epidermal growth factor-induced gene expression of human 12(S)-lipoxygenase [J].
Chen, BK ;
Chang, WC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) :10406-10411
[10]   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