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Neoplasia. 2017 Feb;19(2):84-92. doi: 10.1016/j.neo.2016.12.002. Epub 2017 Jan 5.

SHARPIN Facilitates p53 Degradation in Breast Cancer Cells.

Author information

1
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.
2
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.
3
Department of Gastroenterology, the Third Affiliated Hospital of Xinxiang, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
4
College of Life Science and Technology, Synthetic Biology, Medical Institute, Xinxiang Medical University, Xinxiang 453003, Henan Province, PR China.
5
Department of Pathology, Shandong University School of Medicine, Jinan, PR China.
6
Department of Cancer genomics, LemonData biotech (Shenzhen) Ltd., Shenzhen, PR China.
7
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.
8
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.
9
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.

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.

PMID:
28063307
PMCID:
PMC5219588
DOI:
10.1016/j.neo.2016.12.002
[Indexed for MEDLINE]
Free PMC Article

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