E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene promoter.

Arch Biochem Biophys 2004 Nov;431(1):95-106

Molecular Neuroscience and Bioinformatics Laboratories, Mental Health, Behavioral Science and Research Services, VA Medical Center (151), Louisville, KY 40206, USA.

Human myo-inositol 1-phosphate synthase (IP synthase; E.C. 5.5.1.4), encoded by ISYNA1, catalyzes the de novo synthesis of inositol 1-phosphate from glucose 6-phosphate. It is a potential target for mood-stabilizing drugs such as lithium and valproate. But, very little is known about the regulation of human IP synthase. Here, we have characterized the minimal promoter of ISYNA1 and show that it is upregulated by E2F1. Upregulation occurs in a dose-dependent fashion and can be suppressed by ectopic expression of Rb. EMSA and antibody supershift analysis identified a functional E2F binding motif at -117. Complex formation at this site was competed by an excess of unlabeled Sp1 oligo consistent with the -117 E2F site overlapping an Sp1 motif. Because the -117 E2F motif is not a high-affinity binding site, we propose that the upregulation of ISYNA1 occurs through the cooperative interaction of several low-affinity E2F binding motifs present in the minimal promoter.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.abb.2004.08.002DOI Listing
November 2004
2 Reads

Publication Analysis

Top Keywords

myo-inositol 1-phosphate
8
1-phosphate synthase
8
-117 e2f
8
e2f binding
8
minimal promoter
8
motif -117
8
regulation human
8
human myo-inositol
8
e2f
4
identified functional
4
analysis identified
4
functional e2f
4
complex formation
4
-117 complex
4
supershift analysis
4
binding motif
4
formation site
4
expression emsa
4
e2f1 upregulation
4
upregulation occurs
4

Similar Publications