| RRC ID |
38538
|
| 著者 |
Benoki S, Yoshinari K, Chikada T, Imai J, Yamazoe Y.
|
| タイトル |
Transactivation of ABCG2 through a novel cis-element in the distal promoter by constitutive androstane receptor but not pregnane X receptor in human hepatocytes.
|
| ジャーナル |
Arch Biochem Biophys
|
| Abstract |
A previous report demonstrated that treatment of human hepatocytes with phenobarbital, an activator of nuclear receptor constitutive androstane receptor (CAR), increases mRNA levels of an efflux transporter ABCG2, which is involved in the excretion of xenobiotics in liver and intestine. The results suggest that human CAR (hCAR) transactivates human ABCG2 (hABCG2) expression. In this study, we confirmed increase in ABCG2 mRNA levels in human hepatocytes after adenoviral expression of hCAR and treatment with its activator. Reporter assays suggested the existence of an hCAR-responsive element between -8000 and -7485 of hABCG2 promoter. Electrophoretic mobility shift assays and chromatin immunoprecipitation assays identified a DR5 motif (direct repeat separated by five nucleotides) within the region as a binding motif of hCAR/human retinoid X receptor α heterodimer. The introduction of mutations into the DR5 motif resulted in the complete loss of the hCAR-mediated transactivation. Interestingly, human pregnane X receptor, belonging to the same NR1I subfamily as CAR, did not activate any reporter gene containing the DR5 motif. Taken together, our present findings suggest that hCAR transactivates hABCG2 through the DR5 motif located in its distal promoter in human hepatocytes and that the motif prefers hCAR to pregnane X receptor.
|
| 巻・号 |
517(2)
|
| ページ |
123-30
|
| 公開日 |
2012-1-15
|
| DOI |
10.1016/j.abb.2011.10.014
|
| PII |
S0003-9861(11)00351-1
|
| PMID |
22093699
|
| MeSH |
ATP Binding Cassette Transporter, Subfamily G, Member 2
ATP-Binding Cassette Transporters / genetics*
Amino Acid Motifs
Base Sequence
Binding Sites / genetics
Constitutive Androstane Receptor
DNA Primers / genetics
Genetic Complementation Test
Hep G2 Cells
Hepatocytes / metabolism*
Humans
Mutagenesis, Site-Directed
Neoplasm Proteins / genetics*
Pregnane X Receptor
Promoter Regions, Genetic
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptors, Cytoplasmic and Nuclear / chemistry
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism*
Receptors, Steroid / chemistry
Receptors, Steroid / metabolism*
Recombinant Proteins / chemistry
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Transcriptional Activation
|
| IF |
3.391
|
| 引用数 |
14
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
