Up-regulation of CAR expression through Elk-1 in HepG2 and SW480 cells by serum starvation stress.
Constitutive androstane receptor (CAR) is a transcription factor regulating the expression of several genes related to drug metabolism. CAR expression was elevated in human HepG2 and SW480 cells by serum starvation. From reporter gene assays, mutagenesis, RNA interference, and chromatin immunoprecipitation assays, we identified the serum response element at -142/-139 in the CAR gene transactivated by Elk-1. Whereas treatment with U0126 (ERK inhibitor) enhanced CAR expression, SP600125 (stress-activated protein kinase inhibitor, SAPK) suppressed the phosphorylation of Elk-1 caused by serum-starvation stress and the elevation of CAR mRNA, suggesting that CAR expression may be mediated by phosphorylated Elk-1 via the SAPK signaling pathway.
Osabe
Makoto
M
Department of Pharmaco-Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka 422-8526, Japan.
Sugatani
Junko
J
Takemura
Akiko
A
Kurosawa
Masatoshi
M
Yamazaki
Yasuhiro
Y
Ikari
Akira
A
Miwa
Masao
M
D024506:5' Flanking Region / Q000235:genetics; D000873:Anthracenes / Q000494:pharmacology; D001483:Base Sequence; D045744:Cell Line, Tumor; D000090702:Constitutive Androstane Receptor; D016895:Culture Media, Serum-Free; D006801:Humans; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism*
D000873:Anthracenes; D000090702:Constitutive Androstane Receptor; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; C432165:pyrazolanthrone