title: Jab1 promotes glioma cell proliferation by regulating Siah1/β-catenin pathway.
abstract: Jab1 (Jun activation domain-binding protein 1), also known as CSN5 (COP9 signalosome subunit 5), is frequently overexpressed in several cancer types. However, the biological functions and the molecular mechanisms of the Jab1 protein in human gliomas have not been investigated. In this study, we found that Jab1 protein was increasingly expressed in human glioma tissues comparing with normal brain tissues (Non-tumor). This suggested that Jab1 might be involved in the development of glioma. Thus, the role of Jab1 in glioma cell proliferation was investigated using Jab1 loss- and gain-of-function. The results showed that downregulation of Jab1 significantly inhibited glioma cell proliferation, while overexpression of Jab1 promoted it. Further investigation on molecular targets revealed that silencing of Jab1 obviously increased the p53 protein level thereby promoting the transcription of ubiquitin ligase Siah1 (Seven in absentia homolog 1), which aggravates the degradation of β-catenin. In contrast, overexpression of Jab1 had the opposite effect. Taken together, these findings suggest that Jab1 promotes glioma cell proliferation and increased expression of Jab1 in glioma patients may amplify β-catenin signaling to contribute to glioma cell proliferation.
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
authors.forename: Yufu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|The Graduate School, Xuzhou Medical University, Xuzhou, People's Republic of China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Qiu
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|The Graduate School, Xuzhou Medical University, Xuzhou, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|The Graduate School, Xuzhou Medical University, Xuzhou, People's Republic of China.
authors.forename: Fengyuan
authors.initials: F
authors.lastname: Qian
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|The Graduate School, Xuzhou Medical University, Xuzhou, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China. shihl655@nenu.edu.cn.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China. shihl655@nenu.edu.cn.
authors.forename: Hengliang
authors.initials: H
authors.lastname: Shi
authors.affiliation: Insititute of Nervous System Diseases, Xuzhou Medical University, 84 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China. yu.rutong@163.com.|Brain Hospital, Affiliated Hospital of Xuzhou Medical University, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, People's Republic of China. yu.rutong@163.com.
authors.forename: Rutong
authors.initials: R
authors.lastname: Yu
mesh_terms: D000704:Analysis of Variance; D001932:Brain Neoplasms / Q000473:pathology*; D000075686:COP9 Signalosome Complex / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D003114:Colony-Forming Units Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D005910:Glioma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: C477080:1-(3-dimethylaminopropyl)-3-ethylurea; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D051176:beta Catenin; D049452:Green Fluorescent Proteins; D014508:Urea; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex
keywords: Glioma; Jab1; P53; Siah1; β-Catenin