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Techniques to Induce and Quantify Cellular Senescence
06:51

Techniques to Induce and Quantify Cellular Senescence

Published on: May 1, 2017

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The nuclear receptor RXRA controls cellular senescence by regulating calcium signaling

Xingjie Ma1, Marine Warnier1, Clotilde Raynard1

  • 1Centre de Recherche en Cancérologie de Lyon, Inserm U1052, CNRS UMR 5286, Centre Léon Bérard, Université de Lyon, Lyon, France.

Aging Cell
|September 15, 2018
PubMed

Insights

Retinoid X receptor alpha (RXRA) represses calcium signaling via ITPR2 and MCU, controlling cellular senescence. RXRA regulates reactive oxygen species and DNA damage, impacting aging and cancer pathways.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular senescence is a critical process in development, aging, and disease.
  • Calcium signaling plays a key role in cellular senescence, but its regulation is not fully understood.
  • The inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is involved in senescence, but its regulatory mechanisms are unclear.

Purpose of the Study:

  • To investigate the regulation of inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) expression.
  • To identify factors controlling calcium signaling pathways involved in cellular senescence.

Main Methods:

  • siRNA screen of 160 transcription factors and epigenetic regulators.
  • Analysis of calcium signaling, reactive oxygen species (ROS) production, and DNA damage.
  • Investigated the role of retinoid X receptor alpha (RXRA) in regulating ITPR2 and cellular senescence.

Main Results:

  • Retinoid X receptor alpha (RXRA) was identified as a repressor of ITPR2 expression.
  • RXRA regulates calcium signaling through ITPR2 and the mitochondrial calcium uniporter (MCU).
  • RXRA knockdown induced ROS and DNA damage, triggering senescence via the ITPR2-MCU axis and p53 activation.
  • RXRA overexpression reduced DNA damage and delayed senescence.

Conclusions:

  • RXRA acts as a novel regulator of calcium signaling and cellular senescence.
  • The RXRA-ITPR2-MCU axis influences ROS production, DNA damage, and senescence.
  • Nuclear receptors, specifically RXRA, offer new therapeutic targets for age-related diseases and cancer.
Keywords:
ITPR2calciumnuclear receptorp53senescence

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