DEC1, a basic helix-loop-helix transcription factor and a novel target gene of the p53 family, mediates p53-dependent premature senescence

Yingjuan Qian, Jin Zhang, Bingfang Yan, Xinbin Chen

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Cellular senescence plays an important role in tumor suppression. p53 tumor suppressor has been reported to be crucial in cellular senescence. However, the underlying mechanism is poorly understood. In this regard, a cDNA microarray assay was performed to identify p53 targets involved in senescence. Among the many candidates is DEC1, a basic helix-loop-helix transcription factor that has been recently shown to be up-regulated in K-ras-induced premature senescence. However, it is not clear whether DEC1 is capable of inducing senescence. Here, we found that DEC1 is a novel target gene of the p53 family and mediates p53-dependent premature senescence. Specifically, we showed that DEC1 is induced by the p53 family and DNA damage in a p53-dependent manner. We also found that the p53 family proteins bind to, and activate, the promoter of the DEC1 gene. In addition, we showed that overexpression of DEC1 induces G1 arrest and promotes senescence. Moreover, we found that targeting endogenous DEC1 attenuates p53-mediated premature senescence in response to DNA damage. Furthermore, overexpression of DEC1 induces cellular senescence in p53-knockdown cells, albeit to a lesser extent. Finally, we showed that DEC1-induced senescence is p21-independent. Taken together, our data provided strong evidence that DEC1 is one of the effectors downstream of p53 to promote premature senescence.

Original languageEnglish (US)
Pages (from-to)2896-2905
Number of pages10
JournalJournal of Biological Chemistry
Volume283
Issue number5
DOIs
StatePublished - Feb 1 2008

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Basic Helix-Loop-Helix Transcription Factors
p53 Genes
Tumors
Genes
DNA
Microarrays
Cell Aging
Assays
Complementary DNA
DNA Damage
Proteins
Oligonucleotide Array Sequence Analysis
Neoplasms

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

DEC1, a basic helix-loop-helix transcription factor and a novel target gene of the p53 family, mediates p53-dependent premature senescence. / Qian, Yingjuan; Zhang, Jin; Yan, Bingfang; Chen, Xinbin.

In: Journal of Biological Chemistry, Vol. 283, No. 5, 01.02.2008, p. 2896-2905.

Research output: Contribution to journalArticle

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