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 journalArticlepeer-review

3 Scopus citations

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

ASJC Scopus subject areas

  • Molecular Biology
  • Oncology
  • Cancer Research

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