21 5 28 2007 2008 CARElk
CARPXR CAR CAR EST cdna CAR CAR 10FCS 96 SW480 HepG2 anti-lamin A/C anti-phospho-histone H3 anti-cyclin D1 G1 anti-cyclin A S CAR lamin A/C CAR Fig. 1 Lamin A/C /G1 lamin A/C G1 Cyclin D1 CAR cyclin A CAR I) A1 II) A1 A2 A3 * ** ** B1 B2 B3 A2 Fig. 1 Confocal images of SW480 cells expressing CAR (A1, B1, C1, D1) and lamin A/C (A2), cyclin D1 (B2), cyclin A (C2) or phospho-histone H3 (D2). *, late C1 C2 C3 A3 D1 D2 D3
cytokinesis/early G1; **, late G1. Bar, 10 µm. CAR phospho-histone H3 CAR SW480 S 2 CAR SW480 6 S 10 M Fig. 2A cyclin A cyclin B1cyclin D1cyclin Ephosphorylated RBCDK2 CDK4 RXR Fig. 2 Cell cycle expression of CAR. CAR 2 S M G1 Fig. 2B CAR S G2/Mcyclin D1cyclin Ephosphorylated RB CDK2 CDK4 RXR CAR 2 G1 cyclin B1 Fig. 2CcyclinD1 CDK4 8 CAR Fig. 2C CAR RB 12 14 CDK4 SW480 HepG2 CAR CDK CDK purvalanol A: CDK2CDK5 SU9516: CDK1CDK2CDK4 CDK inhibitor p35: CDK1CDK2 bohomine: CDK1 CAR RXR mrna PCR CDK SU9516 CAR mrna CAR CDK4 SW480 HepG2 anti-cdk4 sirnas anti-cdk4 sirnas SW480 HepG2 CDK4 CAR SW480 anti-car sirnas HepG2 CAR mrna SW480 anti-car sirna CAR mrna 58% HepG2 100% CAR mrna SW480 HepG2 UGT1A1 mrna48% 100%MDM2 mrna 49% 81% anti-car sirnas SW480 HepG2 CAR MDM2
HepG2 SW480 sirnas CAR p21 anti-car sirnas HepG2 CAR BrdU Fig. 3 Effect of HGF on the expression of CAR, MDM2, p53, p21, and p16 in HepG2. CAR HepG2 anti-car sirna HGF CAR Fig. 3D ihgf p16 CDK4 ERK CDK4 CAR iicar p53 MDM2 p53 p21 iiip21 CDK2 HGF p16 CDK4 CDK2 CDK4 p21 p27 CDK2 RB E2F E S DNA Fig. 3D CAR G1 CAR CAR G1 HepG2 CAR mrna UGT1A1 CYP2B6 EGF CAR mrna ERK U0126 PI3-kinase LY204002 CAR ERK PI3-kinase CAR CAR 1 5 CAR CAR 5 12kbp DNA CAR 1 5 0.2kbp DNA ETS SRE1SRE2 SRE1 SRE1SRE2 GR HNF4
CAR 1 5 0.2kbp ETS SRE1SRE 2 ETS ELK Fig.4 ETS ELK ELK SRE 2 SRE1 SRE1SRE2 SRE1 ELK Fig. 4 Elk-1 directly binds to the serum response element on the CAR gene. 6 1. M. Osabe, J. Sugatani, A. Takemura, M. Kurosawa, Y. Yamazaki, A. Ikari, M. Miwa: Up-regulation of CAR expression through Elk-1 in HepG2 and SW480 cells by serum starvation stress. FEBS Letters, 583(5), 885-889 (2009) [IF 3.263] 2. M. Osabe, J. Sugatani, A. Takemura, Y. Yamazaki, A. Ikari, N. Kitamura, M. Negishi, M. Miwa: Expression of CAR in SW480 and HepG2 cells during G1 is associated with cell proliferation. Biochem. Biophys. Res. Commun., 369 (4), 1027-1033 (2008) [IF 2.855] 3. T. Takahashi, Y. Moriyama, A. Ikari, J. Sugatani T. Suzuki, M. Miwa: Surface localization of the nuclear receptor CAR in influenza A virus-infected cells. Biochem. Biophys. Res. Commun., 368(3), 550-555 (2008) [IF 2.855] 4. T. Sueyoshi, R. Moore, J. Sugatani Y. Matsumura, M. Negishi: PPP1R16A, the membrane subunit of protein phosphatase 1b, signals nuclear translocation of the nuclear receptor CAR. Mol. Pharmacol., 73(4), 1113-1121 (2008) [IF 4.469 5. M. Osabe, J. Sugatani, T. Fukuyama, S. Ikushiro, A. Ikari, M. Miwa: Constitutive androstane receptor and peroxisome proliferator-activated receptor a are activated in liver of male rats fed a high-fat and high-sucrose diet and the hepatic expression of UGT1A1 and UGT1A6 is enhanced. Drug Metab. Dispos., 36(2), 294-302 (2008) [IF 3.638] 6. J. Sugatani, K. Mizushima, M. Osabe, K. Yamakawa, S. Kakizaki, H. Takagi, M. Mori, A. Ikari, M. Miwa: Transcriptional regulation of human UGT1A1 gene expression through distal and proximal promoter motifs: implication of defects in the UGT1A1 gene promoter. Naunyn Schmiedebergs Arch. Pharmacol., 377 (4-6), 597-605 (2008) [IF 2.779]
10 1. 129 3p.1882009 3 28 2. 129 3p.1882009 3 28 3 BMB2008 81 p.2052008 12 9 4. UGT1A1 11 P450 3 UGT 2008 10 25 5. Junko Sugatani, Makoto Osabe, Akiko Takemura, Yasuhiro Yamazaki, Akira Ikari, Masao Miwa: Transcriptional regulation of UGT1A1 gene expression and its cell-cycle-dependent ecpression by nuclear receptor CAR The 12th International Glucuronidation and UGT Workshop (Quebec, Canada) 6. 54 p.552008 7 5 7. CAR 128 3p.272008 3 28 8. Makoto Osabe, Junko Sugatani, Tomoaki Fukuyama, Yasuhiro Yamazaki, Akira Ikari, Masao MiwaExpression of CAR and its function associated with cell cycle. 9. Junko Sugatani, Kousuke Mizushima, Makoto Osabe, Tadanobu Takahashi, Akira Ikari, Masao Miwa: Transcriptional regulation of human UGT1A1 gene expression through distal and proximal reporter genes by nuclear receptors. The 5th International Symposium on Receptor Mechanisms, Signal Transduction and Drug Effects, International Receptor Symposium, Shizuoka, Japan, p.108, May 10-11, 2007 10. 127 p.252007 3 30 1 1. 3.1.4.393.1.4.514.6.1.14 pp. 557-559p.8322008