PMID- 32973403
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220417
IS  - 1475-2867 (Print)
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 20
DP  - 2020
TI  - XBP1 negatively regulates CENPF expression via recruiting ATF6alpha to the promoter 
      during ER stress.
PG  - 459
LID - 10.1186/s12935-020-01553-9 [doi]
LID - 459
AB  - BACKGROUND: Centromere protein F (CENPF) is a key component of the kinetochore 
      complex involved in mitosis, cell differentiation and cellular response to 
      stresses. However, the alteration of CENPF in response to endoplasmic reticulum 
      (ER) stress has not been well described. In the present study, we investigate 
      CENPF regulation in response to ER stress. METHODS: Quantitative real-time 
      polymerase chain reaction and western blotting were used to determine CENPF 
      expression under ER stress. Luciferase activity analysis was performed to 
      investigate the promoter regions contributing to CENPF transcription in response 
      to TG. Chromatin immunoprecipitation (ChIP) and ChIP Re-IP assays were used to 
      determine if X-box binding protein 1 (XBP1) and/or activating transcription 
      factor 6alpha (ATF6alpha) bind in the CENPF promoter region. Cell apoptosis and 
      proliferation were analyzed using TUNEL, cell growth and clonogenic assays. 
      RESULTS: CENPF expression is dramatically reduced under ER stress induced by 
      thapsigargin (TG), brefeldin A (BFA), or tunicamycin (TM) and this downregulation 
      of CENPF expression was dependent on XBP1 and ATF6alpha. Luciferase activity analysis 
      of the truncated CENPF promoter indicates that regions from bases - 679 to - 488 
      and from - 241 to - 78 in the CENPF promoter were sensitive to TG treatment. 
      Additionally, ChIP and ChIP Re-IP assays reveal that XBP1 and ATF6alpha were 
      assembled on the same regions of CENPF promoter. Notably, we identify two XBP1 
      binding sequences at positions - 567 and - 192, to which XBP1 binding was 
      enhanced by TG. Finally, CENPF overexpression inhibits cell apoptosis and 
      promotes cell proliferation in response to ER stress. CONCLUSION: In summary, 
      these results demonstrate that ER stress plays a crucial role in CENPF 
      expression, and XBP1 may up-regulate DNA-binding affinities after TG treatment to 
      the promoter of CENPF. These findings may contribute to the understanding of the 
      molecular mechanism of CENPF regulation.
CI  - (c) The Author(s) 2020.
FAU - Shen, Tao
AU  - Shen T
AUID- ORCID: 0000-0003-0497-1122
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, No. 
      36, Sanhao Street, Heping District, Shenyang, 110004 People's Republic of China. 
      GRID: grid.412467.2. ISNI: 0000 0004 1806 3501
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, 110122 People's Republic of China. GRID: 
      grid.412449.e. ISNI: 0000 0000 9678 1884
AD  - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037 USA. GRID: 
      grid.479509.6. ISNI: 0000 0001 0163 8573
FAU - Liang, Shuang
AU  - Liang S
AD  - Department of Laboratory Medicine and Pathology, University of Minnesota, 
      Minneapolis, MN 55455 USA. GRID: grid.17635.36. ISNI: 0000000419368657
FAU - Chen, Zhiguang
AU  - Chen Z
AD  - Department of Orthopedics, Shengjing Hospital of China Medical University, No. 
      36, Sanhao Street, Heping District, Shenyang, 110004 People's Republic of China. 
      GRID: grid.412467.2. ISNI: 0000 0004 1806 3501
LA  - eng
PT  - Journal Article
DEP - 20200922
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
PMC - PMC7507253
OTO - NOTNLM
OT  - ATF6alpha
OT  - CENPF
OT  - ER stress
OT  - Expression regulation
OT  - XBP1
COIS- Competing interestsThe authors declare that they have no competing interests.
EDAT- 2020/09/26 06:00
MHDA- 2020/09/26 06:01
PMCR- 2020/09/22
CRDT- 2020/09/25 06:00
PHST- 2020/05/13 00:00 [received]
PHST- 2020/09/11 00:00 [accepted]
PHST- 2020/09/25 06:00 [entrez]
PHST- 2020/09/26 06:00 [pubmed]
PHST- 2020/09/26 06:01 [medline]
PHST- 2020/09/22 00:00 [pmc-release]
AID - 1553 [pii]
AID - 10.1186/s12935-020-01553-9 [doi]
PST - epublish
SO  - Cancer Cell Int. 2020 Sep 22;20:459. doi: 10.1186/s12935-020-01553-9. eCollection 
      2020.