JMJD5 interacts with p53 and negatively regulates p53 function in control of cell cycle and proliferation

Xiaobin Huang, Shuilian Zhang, Hongyan Qi, Zhengyang Wang, Hongwu Chen, Jimin Shao, Jing Shen

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

JMJD5 is a Jumonji C domain-containing demethylase/hydroxylase shown to be essential in embryological development, osteoclastic maturation, circadian rhythm regulation and cancer metabolism. However, its role and underlying mechanisms in oncogenesis remain unclear. Here, we demonstrate that JMJD5 forms complex with the tumor suppressor p53 by interacting with p53 DNA-binding domain (DBD), and negatively regulates its activity. Downregulation of JMJD5 resulted in increased expression of multiple p53 downstream genes, such as the cell cycle inhibitor CDKN1A and DNA repair effector P53R2, only in p53-proficient lung cancer cells. Upon DNA damage, the JMJD5-p53 association decreased, and thereby, promoted p53 recruitment to the target genes and stimulated its transcriptional activity. Furthermore, JMJD5 facilitated the cell cycle progression in a p53-dependent manner under both normal and DNA damage conditions. Depletion of JMJD5 inhibited cell proliferation and enhanced adriamycin-induced cell growth suppression in the presence of p53. Collectively, our results reveal that JMJD5 is a novel binding partner of p53 and it functions as a positive modulator of cell cycle and cell proliferation mainly through the repression of p53 pathway. Our study extends the mechanistic understanding of JMJD5 function in cancer development and implicates JMJD5 as a potential therapeutic target for cancer.

Original languageEnglish (US)
Pages (from-to)2286-2295
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1853
Issue number10
DOIs
StatePublished - 2015

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Cell Proliferation
Cell Cycle
DNA Damage
Neoplasms
p53 Genes
Circadian Rhythm
Mixed Function Oxygenases
DNA Repair
Doxorubicin
Lung Neoplasms
Carcinogenesis
Down-Regulation
DNA
Growth
Genes
Therapeutics

Keywords

  • Cancer development
  • Cell cycle
  • Gene transcription
  • JMJD5
  • P53 tumor suppressor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

JMJD5 interacts with p53 and negatively regulates p53 function in control of cell cycle and proliferation. / Huang, Xiaobin; Zhang, Shuilian; Qi, Hongyan; Wang, Zhengyang; Chen, Hongwu; Shao, Jimin; Shen, Jing.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1853, No. 10, 2015, p. 2286-2295.

Research output: Contribution to journalArticle

Huang, Xiaobin ; Zhang, Shuilian ; Qi, Hongyan ; Wang, Zhengyang ; Chen, Hongwu ; Shao, Jimin ; Shen, Jing. / JMJD5 interacts with p53 and negatively regulates p53 function in control of cell cycle and proliferation. In: Biochimica et Biophysica Acta - Molecular Cell Research. 2015 ; Vol. 1853, No. 10. pp. 2286-2295.
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