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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells
CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국독성학회 Toxicological Research Toxicological Research Vol.33 No.3 KCI등재 SCOPUS
- 발행연도
- 2017.6
- 수록면
- 211 - 218 (8page)
이용수
CYP1B1 Activates Wnt/β-Catenin Signaling through Suppression of Herc5-Mediated ISGylation for Protein Degradation on β-Catenin in HeLa Cells
초록· 키워드
오류제보하기
Cytochrome P450 1B1 (CYP1B1) acts as a hydroxylase for estrogen and activates potential carcinogens. Moreover, its expression in tumor tissues is much higher than that in normal tissues. Despite this association between CYP1B1 and cancer, the detailed molecular mechanism of CYP1B1 on cancer progression in HeLa cells remains unknown. Previous reports indicated that the mRNA expression level of Herc5, an E3 ligase for ISGylation, is promoted by CYP1B1 suppression using specific small interfering RNA, and that ISGylation may be involved in ubiquitination related to β-catenin degradation. With this background, we investigated the relationships among CYP1B1, Herc5, and β-catenin. RT-PCR and western blot analyses showed that CYP1B1 overexpression induced and CYP1B1 inhibition reduced, respectively, the expression of Wnt/β-catenin signaling target genes including β-catenin and cyclin D1. Moreover, HeLa cells were treated with the CYP1B1 inducer 7,12-dimethylbenz[α]anthracene (DMBA) or the CYP1B1 specific inhibitor, tetramethoxystilbene (TMS) and consequently DMBA increased and TMS decreased β-catenin and cyclin D1 expression, respectively. To determine the correlation between CYP1B1 expression and ISGylation, the expression of ISG15, a ubiquitin-like protein, was detected following CYP1B1 regulation, which revealed that CYP1B1 may inhibit ISGylation through suppression of ISG15 expression. In addition, the mRNA and protein expression levels of Herc5 were strongly suppressed by CYP1B1. Finally, an immunoprecipitation assay revealed a direct physical interaction between Herc5 and β-catenin in HeLa cells. In conclusion, these data suggest that CYP1B1 may activate Wnt/β-catenin signaling through stabilization of β-catenin protein from Herc5-mediated ISGylation for proteosomal degradation.
목차
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGMENTS
REFERENCES
참고문헌 (33)
참고문헌 신청
Nelson, D. R / 1996 / P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature / Pharmacogenetics 6:1~42
Yang, X / 2010 / Systematic genetic and genomic analysis of cytochrome P450enzyme activities in human liver / Genome Res 20:1020~1036
Tsutomu Shimada / 2017 / Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity / 한국독성학회지 33(2):79~96
Saini, / 2009 / Functional significance of cytochrome P450 1B1 in endometrial carcinogenesis / Cancer Res 69:7038~7045
Delvoux, B / 2009 / Increased production of 17β-estradiol in endometriosis lesions is the result of impaired metabolism / J. Clin. Endocrinol. Metab 94:876~883
Yang, X / 2010 / Systematic genetic and genomic analysis of cytochrome P450enzyme activities in human liver / Genome Res 20:1020~1036
Tsutomu Shimada / 2017 / Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity / 한국독성학회지 33(2):79~96
Saini, / 2009 / Functional significance of cytochrome P450 1B1 in endometrial carcinogenesis / Cancer Res 69:7038~7045
Delvoux, B / 2009 / Increased production of 17β-estradiol in endometriosis lesions is the result of impaired metabolism / J. Clin. Endocrinol. Metab 94:876~883
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UCI(KEPA) : I410-ECN-0101-2018-513-001055131