PMID- 28652211 OWN - NLM STAT- MEDLINE DCOM- 20171120 LR - 20211204 IS - 1878-5875 (Electronic) IS - 1357-2725 (Linking) VI - 89 DP - 2017 Aug TI - CHOP negatively regulates Polo-like kinase 2 expression via recruiting C/EBPalpha to the upstream-promoter in human osteosarcoma cell line during ER stress. PG - 207-215 LID - S1357-2725(17)30150-4 [pii] LID - 10.1016/j.biocel.2017.06.012 [doi] AB - Polo-like kinase 2 (Plk2) is a member of the serine/threonine protein kinase family involved in cell-cycle regulation and cellular response to stresses. However, the alteration of Plk2 in response to endoplasmic reticulum (ER) stress has not been well described. In the present study, we focused on the regulation of Plk2 regulation in response to ER stress. Plk2 expression was dramatically decreased under ER stress induced by brefeldin A (BFA), thapsigargin (TG), or tunicamycin (TM), and this down regulation of Plk2 expression was dependent on activating transcription factor 4 (ATF4) and C/EBP homology protein (CHOP). Luciferase activity analysis of the truncated Plk2 promoter indicated that regions from -2506 to -1806 and from -1002 to -830 of the Plk2 promoter were sensitive to BFA. Additionally, ChIP and ChIP Re-IP assays showed that CHOP and C/EBPalpha were assembled on the same region of Plk2 promoter. Notably, we identified two C/EBPalpha responsive elements at positions -2002 and -948, to which C/EBPalpha or CHOP binding was enhanced by BFA under in vitro and in vivo conditions. Finally, overexpression of Plk2 inhibits cell apoptosis and promotes cell proliferation in response to ER stress. In summary, these results demonstrated that ER stress plays a crucial role in Plk2 expression. CHOP may up-regulate DNA-binding affinities after BFA treatment, via recruiting C/EBPalpha to the upstream-promoter of Plk2. These findings may contribute to the understanding of the molecular mechanism of Plk2 regulation. CI - Copyright (c) 2017 Elsevier Ltd. All rights reserved. FAU - Shen, Tao AU - Shen T AD - Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. Electronic address: shent@sj-hospital.org. FAU - Li, Yan AU - Li Y AD - Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, People's Republic of China. FAU - Chen, Zhiguang AU - Chen Z AD - Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. FAU - Liang, Shuang AU - Liang S AD - Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455, USA. FAU - Guo, Zhouyang AU - Guo Z AD - Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. FAU - Wang, Ping AU - Wang P AD - Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001, People's Republic of China. FAU - Wu, Qijun AU - Wu Q AD - Department of Clinical Epidemiology, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. FAU - Ba, Gen AU - Ba G AD - Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. FAU - Fu, Qin AU - Fu Q AD - Department of Orthopedic Surgery, Shengjing Hospital, China Medical University, Shenyang 110004, People's Republic of China. LA - eng PT - Journal Article DEP - 20170624 PL - Netherlands TA - Int J Biochem Cell Biol JT - The international journal of biochemistry & cell biology JID - 9508482 RN - 0 (ATF4 protein, human) RN - 0 (CCAAT-Enhancer-Binding Protein-alpha) RN - 145891-90-3 (Activating Transcription Factor 4) RN - 147336-12-7 (Transcription Factor CHOP) RN - EC 2.7.11.- (PLK2 protein, human) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) SB - IM MH - Activating Transcription Factor 4/metabolism MH - Apoptosis/genetics MH - CCAAT-Enhancer-Binding Protein-alpha/*metabolism MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Endoplasmic Reticulum Stress/*genetics MH - *Gene Expression Regulation, Neoplastic MH - Humans MH - Mutagenesis MH - Nucleotide Motifs/genetics MH - Osteosarcoma/*pathology MH - Promoter Regions, Genetic/genetics MH - Protein Serine-Threonine Kinases/*genetics MH - Protein Transport MH - Transcription Factor CHOP/*metabolism MH - Transcription, Genetic OTO - NOTNLM OT - C/EBPalpha OT - CHOP OT - ER stress OT - Expression regulation OT - Plk2 EDAT- 2017/06/28 06:00 MHDA- 2017/11/29 06:00 CRDT- 2017/06/28 06:00 PHST- 2016/12/22 00:00 [received] PHST- 2017/06/09 00:00 [revised] PHST- 2017/06/22 00:00 [accepted] PHST- 2017/06/28 06:00 [pubmed] PHST- 2017/11/29 06:00 [medline] PHST- 2017/06/28 06:00 [entrez] AID - S1357-2725(17)30150-4 [pii] AID - 10.1016/j.biocel.2017.06.012 [doi] PST - ppublish SO - Int J Biochem Cell Biol. 2017 Aug;89:207-215. doi: 10.1016/j.biocel.2017.06.012. Epub 2017 Jun 24.