| RRC ID |
39440
|
| 著者 |
Kido S, Miyamoto K, Mizobuchi H, Taketani Y, Ohkido I, Ogawa N, Kaneko Y, Harashima S, Takeda E.
|
| タイトル |
Identification of regulatory sequences and binding proteins in the type II sodium/phosphate cotransporter NPT2 gene responsive to dietary phosphate.
|
| ジャーナル |
J Biol Chem
|
| Abstract |
Dietary phosphate (P(i)) is a most important regulator for renal P(i) reabsorption. The type II sodium-dependent phosphate (Na/P(i)) cotransporters (NPT2) are located at the apical membranes of renal proximal tubular cells and major functional transporters associated with renal P(i) reabsorption. The consumption of a low-P(i) diet induces the synthesis of NPT2, whereas a high P(i) diet decreases it. The molecular mechanisms of regulation by dietary P(i) are not yet known. In this report, in weaning mice fed a low-P(i) diet for 4 days, the NPT2 mRNA level was increased 1.8-fold compared with mice fed a normal P(i) diet. This increase was due to an elevation of the transcriptional activity. In the NPT2 gene promoter, the DNA footprint analysis showed that six regions were masked by the binding protein, but at the position -1010 to -985 upstream of the transcription start site, the binding clearly responded to the levels of dietary P(i). The phosphate response element (PRE) of the NPT2 gene was found to consist of the motif related to the E box, 5'-CACGTG-3'. A yeast one-hybrid system was used to clone a transcription factor that binds to the PRE sequences in the proximal promoter of the NPT2 gene. Two cDNA clones that encoded protein of the mouse transcription factor muE3 (TFE3) were isolated. This is a DNA-binding protein that activates transcription through the muE3 site of the immunoglobulin heavy chain enhancer. TFE3 antibody completely inhibited the binding to the PRE. The coexpression of TFE3 in COS-7 cells transfected with the NPT2 gene promoter markedly stimulated the transcriptional activity. The feeding of a low P(i) diet significantly increased the amount of TFE3 mRNA in the kidney. These findings suggest that TFE3 may participate in the transcriptional regulation of the NPT2 gene by dietary P(i).
|
| 巻・号 |
274(40)
|
| ページ |
28256-63
|
| 公開日 |
1999-10-1
|
| DOI |
10.1074/jbc.274.40.28256
|
| PII |
S0021-9258(19)52044-0
|
| PMID |
10497181
|
| MeSH |
Animals
Base Sequence
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
COS Cells
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cloning, Molecular
DNA
DNA-Binding Proteins / genetics
Diet*
Gene Expression Regulation
Male
Mice
Mice, Inbred ICR
Molecular Sequence Data
Phosphates / administration & dosage*
Promoter Regions, Genetic
RNA, Messenger / genetics
RNA, Messenger / metabolism
Regulatory Sequences, Nucleic Acid*
Sodium-Phosphate Cotransporter Proteins
Sodium-Phosphate Cotransporter Proteins, Type I
Sodium-Phosphate Cotransporter Proteins, Type II
Sodium-Phosphate Cotransporter Proteins, Type III
Symporters*
Transcription Factors / genetics
Transcriptional Activation
|
| IF |
4.238
|
| 引用数 |
60
|
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
COS-7(RCB0539) |
