Abstract
Differentiated embryonic chondrocyte expressed gene 1 (DEC1, also known as Sharp2/Stra13/BHLHE40) is a basic helix-loop-helix transcription factor that plays an important role in circadian rhythms, cell proliferation, apoptosis, cellular senescence, hypoxia response, and epithelial-tomesenchymal transition of tumor cells. Secretory clusterin (sCLU) is a cytoprotective protein that guards against genotoxic stresses. Here, clusterin (CLU) was identified as a novel target gene of DEC1 and suppresses DNA damage- induced cell death in tumor cells. Mechanistically, based on chromatin immunoprecipitation and luciferase assays, DEC1 binds to and activates the promoter of the CLU gene. DEC1 and DNA-damaging agents induce sCLU expression, whereas DEC1 knockdown decreases the expression of sCLU upon DNA damage. Moreover, the data demonstrate that DEC1 inhibits, whereas sCLU knockdown enhances, DNA damage-induced cell death in MCF7 breast cancer cells. Given that DEC1 and sCLU are frequently overexpressed in breast cancers, these data providemechanistic insight into DEC1 as a prosurvival factor by upregulating sCLU to reduce the DNA damage-induced apoptotic response. Together, this study reveals sCLU as a novel target of DEC1 which modulates the sensitivity of the DNA damage response.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1641-1651 |
| Number of pages | 11 |
| Journal | Molecular Cancer Research |
| Volume | 16 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2018 |
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ASJC Scopus subject areas
- Molecular Biology
- Oncology
- Cancer Research
Cite this
Clusterin, a novel DEC1 target, modulates DNA damage-mediated cell death. / Ming, Xin; Bao, Chenyi; Hong, Tao; Yang, Ying; Chen, Xinbin; Jung, Yong Sam; Qian, Yingjuan.
In: Molecular Cancer Research, Vol. 16, No. 11, 01.11.2018, p. 1641-1651.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clusterin, a novel DEC1 target, modulates DNA damage-mediated cell death
AU - Ming, Xin
AU - Bao, Chenyi
AU - Hong, Tao
AU - Yang, Ying
AU - Chen, Xinbin
AU - Jung, Yong Sam
AU - Qian, Yingjuan
PY - 2018/11/1
Y1 - 2018/11/1
N2 - Differentiated embryonic chondrocyte expressed gene 1 (DEC1, also known as Sharp2/Stra13/BHLHE40) is a basic helix-loop-helix transcription factor that plays an important role in circadian rhythms, cell proliferation, apoptosis, cellular senescence, hypoxia response, and epithelial-tomesenchymal transition of tumor cells. Secretory clusterin (sCLU) is a cytoprotective protein that guards against genotoxic stresses. Here, clusterin (CLU) was identified as a novel target gene of DEC1 and suppresses DNA damage- induced cell death in tumor cells. Mechanistically, based on chromatin immunoprecipitation and luciferase assays, DEC1 binds to and activates the promoter of the CLU gene. DEC1 and DNA-damaging agents induce sCLU expression, whereas DEC1 knockdown decreases the expression of sCLU upon DNA damage. Moreover, the data demonstrate that DEC1 inhibits, whereas sCLU knockdown enhances, DNA damage-induced cell death in MCF7 breast cancer cells. Given that DEC1 and sCLU are frequently overexpressed in breast cancers, these data providemechanistic insight into DEC1 as a prosurvival factor by upregulating sCLU to reduce the DNA damage-induced apoptotic response. Together, this study reveals sCLU as a novel target of DEC1 which modulates the sensitivity of the DNA damage response.
AB - Differentiated embryonic chondrocyte expressed gene 1 (DEC1, also known as Sharp2/Stra13/BHLHE40) is a basic helix-loop-helix transcription factor that plays an important role in circadian rhythms, cell proliferation, apoptosis, cellular senescence, hypoxia response, and epithelial-tomesenchymal transition of tumor cells. Secretory clusterin (sCLU) is a cytoprotective protein that guards against genotoxic stresses. Here, clusterin (CLU) was identified as a novel target gene of DEC1 and suppresses DNA damage- induced cell death in tumor cells. Mechanistically, based on chromatin immunoprecipitation and luciferase assays, DEC1 binds to and activates the promoter of the CLU gene. DEC1 and DNA-damaging agents induce sCLU expression, whereas DEC1 knockdown decreases the expression of sCLU upon DNA damage. Moreover, the data demonstrate that DEC1 inhibits, whereas sCLU knockdown enhances, DNA damage-induced cell death in MCF7 breast cancer cells. Given that DEC1 and sCLU are frequently overexpressed in breast cancers, these data providemechanistic insight into DEC1 as a prosurvival factor by upregulating sCLU to reduce the DNA damage-induced apoptotic response. Together, this study reveals sCLU as a novel target of DEC1 which modulates the sensitivity of the DNA damage response.
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UR - http://www.scopus.com/inward/citedby.url?scp=85055915038&partnerID=8YFLogxK
U2 - 10.1158/1541-7786.MCR-18-0070
DO - 10.1158/1541-7786.MCR-18-0070
M3 - Article
C2 - 30002194
AN - SCOPUS:85055915038
VL - 16
SP - 1641
EP - 1651
JO - Molecular Cancer Research
JF - Molecular Cancer Research
SN - 1541-7786
IS - 11
ER -