PMID- 27534417 OWN - NLM STAT- MEDLINE DCOM- 20180510 LR - 20191210 IS - 1559-1182 (Electronic) IS - 0893-7648 (Linking) VI - 54 IP - 7 DP - 2017 Sep TI - The Ubiquitin Ligase COP1 Promotes Glioma Cell Proliferation by Preferentially Downregulating Tumor Suppressor p53. PG - 5008-5016 LID - 10.1007/s12035-016-0033-x [doi] AB - 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. FAU - Zou, Shenshan AU - Zou S AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - The Graduate School, Xuzhou Medical College, Xuzhou, China. FAU - Zhu, Yufu AU - Zhu Y AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. FAU - Wang, Bin AU - Wang B AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - The Graduate School, Xuzhou Medical College, Xuzhou, China. FAU - Qian, Fengyuan AU - Qian F AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - The Graduate School, Xuzhou Medical College, Xuzhou, China. FAU - Zhang, Xiang AU - Zhang X AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - The Graduate School, Xuzhou Medical College, Xuzhou, China. FAU - Wang, Lei AU - Wang L AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. FAU - Fu, Chunling AU - Fu C AD - Institute of Blood Diseases, Xuzhou Medical College, Xuzhou, China. FAU - Bao, Hanmo AU - Bao H AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - The Graduate School, Xuzhou Medical College, Xuzhou, China. FAU - Xie, Manyi AU - Xie M AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. FAU - Gao, Shangfeng AU - Gao S AD - Insititute of Nervous System Diseases, Xuzhou Medical College, 84 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. AD - Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, Jiangsu, 221002, People's Republic of China. FAU - Yu, Rutong AU - Yu R AD - 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. AD - 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. FAU - Shi, Hengliang AU - Shi H AD - 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. AD - 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. LA - eng PT - Journal Article DEP - 20160817 PL - United States TA - Mol Neurobiol JT - Molecular neurobiology JID - 8900963 RN - 0 (RNA, Small Interfering) RN - 0 (TP53 protein, human) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Ubiquitin) RN - EC 2.3.2.27 (COP1 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) SB - IM MH - *Cell Proliferation/physiology MH - Down-Regulation MH - Glioma/*metabolism/pathology MH - Humans MH - RNA, Small Interfering/genetics MH - Transcriptional Activation MH - Tumor Suppressor Protein p53/*metabolism MH - Ubiquitin/*metabolism MH - Ubiquitin-Protein Ligases/*metabolism OTO - NOTNLM OT - C-JUN OT - COP1 OT - Glioma OT - Ubiquitin ligase OT - p53 EDAT- 2016/08/19 06:00 MHDA- 2018/05/11 06:00 CRDT- 2016/08/19 06:00 PHST- 2016/03/23 00:00 [received] PHST- 2016/08/01 00:00 [accepted] PHST- 2016/08/19 06:00 [pubmed] PHST- 2018/05/11 06:00 [medline] PHST- 2016/08/19 06:00 [entrez] AID - 10.1007/s12035-016-0033-x [pii] AID - 10.1007/s12035-016-0033-x [doi] PST - ppublish SO - Mol Neurobiol. 2017 Sep;54(7):5008-5016. doi: 10.1007/s12035-016-0033-x. Epub 2016 Aug 17.