Clusterin, a novel DEC1 target, modulates DNA damage-mediated cell death

Xin Ming, Chenyi Bao, Tao Hong, Ying Yang, Xinbin Chen, Yong Sam Jung, Yingjuan Qian

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1641-1651
Number of pages11
JournalMolecular Cancer Research
Volume16
Issue number11
DOIs
StatePublished - Nov 1 2018

Fingerprint

Clusterin
DNA Damage
Cell Death
Breast Neoplasms
Genes
Basic Helix-Loop-Helix Transcription Factors
Cell Hypoxia
Chromatin Immunoprecipitation
Cell Aging
Chondrocytes
Circadian Rhythm
Luciferases
Neoplasms
Cell Proliferation
Apoptosis

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 journalArticle

Ming, Xin ; Bao, Chenyi ; Hong, Tao ; Yang, Ying ; Chen, Xinbin ; Jung, Yong Sam ; Qian, Yingjuan. / Clusterin, a novel DEC1 target, modulates DNA damage-mediated cell death. In: Molecular Cancer Research. 2018 ; Vol. 16, No. 11. pp. 1641-1651.
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