title: SHARPIN Facilitates p53 Degradation in Breast Cancer Cells.
abstract: The ubiquitin binding protein SHAPRIN is highly expressed in human breast cancer, one of the most frequent female malignancies worldwide. Here, we perform SHARPIN depletion in breast cancer cells together with RNA sequencing. The global expression profiling showed p53 signaling as a potential SHARPIN target. SHARPIN depletion decreased cell proliferation, which effect could be rescue by p53 knocking down. Depletion SHARPIN significantly increases p53 protein level and its target genes in multiple breast cancer cell lines. Further experiment revealed that SHARPIN could facilitate p53 poly-ubiquitination and degradation in MDM2 dependent manner. Immuno-precipitation assay showed that SHARPIN associated with MDM2 and prolonged MDM2 protein stability. Analysis of public available database showed SHARPIN correlated with poor prognosis specifically in p53 wild-type breast cancer patients. Together, our finding revealed a novel modifier for p53/MDM2 complex and suggested SHARPIN as a promising target to restore p53 function in breast cancer.
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Huijie
authors.initials: H
authors.lastname: Yang
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education) Department of Renal Cancer and Melanoma, Peking University School of Oncology, Beijing Cancer Hospital and Institute, Beijing, China.
authors.forename: Sifan
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, the Third Affiliated Hospital of Xinxiang, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Weilong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Yingxiang
authors.initials: Y
authors.lastname: Hou
authors.affiliation: College of Life Science and Technology, Synthetic Biology, Medical Institute, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology, Shandong University School of Medicine, Jinan, PR China.
authors.forename: Kun
authors.initials: K
authors.lastname: Mu
authors.affiliation: Department of Cancer genomics, LemonData biotech (Shenzhen) Ltd., Shenzhen, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Niu
authors.affiliation: Department of Cancer genomics, LemonData biotech (Shenzhen) Ltd., Shenzhen, PR China.
authors.forename: Juntao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China. Electronic address: wanghui@xxmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China. Electronic address: zhujian1204@yahoo.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Research Center for Immunology, School of Laboratory Medicine, Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China. Electronic address: 77090993@qq.com.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhuang
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D011379:Prognosis; D055550:Protein Stability; D059748:Proteolysis; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism*
chemical_list: C575183:SHARPIN protein, human; D016159:Tumor Suppressor Protein p53; D014452:Ubiquitins; D051736:Proto-Oncogene Proteins c-mdm2