PMID- 31926341
OWN - NLM
STAT- MEDLINE
DCOM- 20200407
LR  - 20211204
IS  - 1876-4320 (Electronic)
IS  - 1874-9399 (Linking)
VI  - 1863
IP  - 2
DP  - 2020 Feb
TI  - Activating transcription factor 6 (ATF6) negatively regulates Polo-like kinase 4 
      expression via recruiting C/EBPbeta to the upstream-promoter during ER stress.
PG  - 194488
LID - S1874-9399(19)30363-3 [pii]
LID - 10.1016/j.bbagrm.2020.194488 [doi]
AB  - Polo-like kinase 4 (PLK4) is a member of the serine/threonine protein kinase 
      family involved in cell-cycle regulation and cellular response to stresses. 
      However, the alteration of PLK4 in response to endoplasmic reticulum (ER) stress 
      has not been well described. In the present study, we focused on the regulation 
      of PLK4 regulation in response to ER stress. PLK4 expression was dramatically 
      reduced under ER stress induced by brefeldin A (BFA), tunicamycin (TM), or 
      thapsigargin (TG) and down regulation of PLK4 expression was dependent on 
      activating transcription factor 6 (ATF6) and CCAAT/enhancer-binding protein beta 
      (C/EBPbeta). Luciferase activity analysis of the truncated PLK4 promoter indicated 
      that region from -1343 to -1250 of the PLK4 promoter was sensitive to BFA or TG. 
      Additionally, ChIP and ChIP Re-IP assays showed that ATF6 and C/EBPbeta were 
      assembled on the same region of Plk4 promoter. Notably, we identified one C/EBPbeta 
      responsive element at position -1284, to which ATF6 or C/EBPbeta binding was 
      enhanced by BFA or TG under in vitro and in vivo conditions. Finally, 
      overexpression of PLK4 inhibits apoptosis and promotes cell proliferation in 
      response to ER stress. In summary, these results demonstrated that ER stress 
      plays a crucial role in PLK4 expression. ATF6 may upregulate DNA-binding 
      affinities after BFA treatment, via recruiting C/EBPbeta to the upstream promoter of 
      PLK4. These findings may contribute to the understanding of the molecular 
      mechanism of PLK4 regulation.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Shen, Tao
AU  - Shen T
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, People's Republic China. Electronic address: 
      shent@sj-hospital.org.
FAU - Li, Yan
AU  - Li Y
AD  - Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public 
      Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, 
      China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122, 
      Shenyang, Liaoning, People's Republic of China; Sanford Burnham Prebys Medical 
      Discovery Institute, La Jolla, CA 92037, USA.
FAU - Chen, Zhiguang
AU  - Chen Z
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, People's Republic China.
FAU - Liang, Shuang
AU  - Liang S
AD  - Department of Laboratory Medicine & Pathology, University of Minnesota, 
      Minneapolis, MN 55455, USA.
FAU - Qiu, Yu
AU  - Qiu Y
AD  - Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public 
      Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, 
      China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122, 
      Shenyang, Liaoning, People's Republic of China.
FAU - Zhu, Lin
AU  - Zhu L
AD  - Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public 
      Health, and Key Laboratory of Medical Cell Biology of Ministry of Education, 
      China Medical University, No. 77, Puhe Road, Shenyang North New Area, 110122, 
      Shenyang, Liaoning, People's Republic of China.
FAU - Ba, Gen
AU  - Ba G
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, People's Republic China.
FAU - Lu, Guangwei
AU  - Lu G
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, People's Republic China.
FAU - Qiu, Lian
AU  - Qiu L
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, 
      Shenyang 110004, People's Republic China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200109
PL  - Netherlands
TA  - Biochim Biophys Acta Gene Regul Mech
JT  - Biochimica et biophysica acta. Gene regulatory mechanisms
JID - 101731723
RN  - 0 (ATF6 protein, human)
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - EC 2.7.1.- (PLK4 protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
SB  - IM
MH  - Activating Transcription Factor 6/*metabolism
MH  - Apoptosis
MH  - Bone Neoplasms/enzymology/*genetics/metabolism
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Endoplasmic Reticulum Stress/*genetics
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mutagenesis
MH  - Osteosarcoma/enzymology/*genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - Response Elements
MH  - Transcription, Genetic
OTO - NOTNLM
OT  - ATF6
OT  - C/EBPbeta
OT  - ER stress
OT  - Expression regulation
OT  - PLK4
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/01/12 06:00
MHDA- 2020/04/09 06:00
CRDT- 2020/01/12 06:00
PHST- 2019/09/18 00:00 [received]
PHST- 2019/12/26 00:00 [revised]
PHST- 2020/01/07 00:00 [accepted]
PHST- 2020/01/12 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2020/01/12 06:00 [entrez]
AID - S1874-9399(19)30363-3 [pii]
AID - 10.1016/j.bbagrm.2020.194488 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Gene Regul Mech. 2020 Feb;1863(2):194488. doi: 
      10.1016/j.bbagrm.2020.194488. Epub 2020 Jan 9.