title: The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53.
abstract: Human glioma causes substantial morbidity and mortality worldwide. However, the molecular mechanisms underlying glioma progression are still largely unknown. COP1 (constitutively photomorphogenic 1), an E3 ubiquitin ligase, is important in cell survival, development, cell growth, and cancer biology by regulating different substrates. As is well known, both tumor suppressor p53 and oncogenic protein c-JUN could be ubiquitinated and degraded by ubiquitin ligase COP1, which may be the reason that COP1 serves as an oncogene or a tumor suppressor in different cancer types. Up to now, the possible role of COP1 in human glioma is still unclear. In the present study, we found that the expression of COP1 was upregulated in human glioma tissues. The role of COP1 in glioma cell proliferation was investigated using COP1 loss- and gain-of-function. The results showed that downregulation of COP1 by short hairpin RNA (shRNA) inhibited glioma cell proliferation, while overexpression of COP1 significantly promoted it. Furthermore, we demonstrated that COP1 only interacted with and regulated p53, but not c-JUN. Taken together, these results indicate that COP1 may play a role in promoting glioma cell proliferation by interacting with and downregulating tumor suppressor p53 rather than oncogenic protein c-JUN.
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, China.
authors.forename: Shenshan
authors.initials: S
authors.lastname: Zou
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Qian
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Blood Diseases, Xuzhou Medical College, Xuzhou, China.
authors.forename: Chunling
authors.initials: C
authors.lastname: Fu
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|The Graduate School, Xuzhou Medical College, Xuzhou, China.
authors.forename: Hanmo
authors.initials: H
authors.lastname: Bao
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors.forename: Manyi
authors.initials: M
authors.lastname: Xie
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China.
authors.forename: Shangfeng
authors.initials: S
authors.lastname: Gao
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. yu.rutong@163.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. yu.rutong@163.com.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. shl@xzmc.edu.cn.|Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. shl@xzmc.edu.cn.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D005910:Glioma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C471981:COP1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: C-JUN; COP1; Glioma; Ubiquitin ligase; p53