title: p53 negatively regulates Pin1 expression under ER stress.
abstract: Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays a major role in the development of many diseases. A previous study indicated that the apoptotic regulator p53 is significantly increased in response to ER stress and participates in ER stress-induced apoptosis. However, the regulators of p53 expression during ER stress are still not fully understood. Here, we investigated whether p53 contributes to the impairment of Pin1 signaling under ER stress. We found that treatment with thapsigargin, a stimulator of p53 expression and an inducer of ER stress, decreased Pin1 expression in HCT116 cells. Also, we identified functional p53 response elements (p53REs) in the Pin1 promoter. Overexpression of p53 significantly decreased Pin1 expression in HCT116 cells while abolition of p53 gene expression induced Pin1 expression. Pin1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-α or down-regulation of p53 expression. Taken together, ER stress decreased Pin1 expression through p53 activation, and this mechanism may be associated with ER stress-induced cell death. These data reported here support the importance of Pin1 as a potential target molecule mediating tumor development.
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Kwon
authors.initials: K
authors.lastname: Jeong
authors.affiliation: Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Seong-Jin
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Yoojung
authors.initials: Y
authors.lastname: Oh
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hunsung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Young-Seok
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Byung-Su
authors.initials: BS
authors.lastname: Kwon
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sanghyun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Neurology, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Key-Chung
authors.initials: KC
authors.lastname: Park
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Kyung-Sik
authors.initials: KS
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Insug
authors.initials: I
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology (BK21 Project), Medical Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: wchoe@khu.ac.kr.
authors.forename: Wonchae
authors.initials: W
authors.lastname: Choe
mesh_terms: D017209:Apoptosis; D002470:Cell Survival; D002478:Cells, Cultured; D059865:Endoplasmic Reticulum Stress; D015971:Gene Expression Regulation, Enzymologic; D045325:HCT116 Cells; D006801:Humans; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000096:biosynthesis* / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D016159:Tumor Suppressor Protein p53; C000606846:PIN1 protein, human
keywords: ER stress; Pifithrin-α; Pin1; p53; p53REs