Early growth response 2 (EGR2) is a novel regulator of the senescence programme

Eleanor J Tyler1, Ana Gutierrez Del Arroyo2, Bethany K Hughes1

  • 1Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Aging Cell
|February 6, 2021
PubMed

Insights

Early growth response 2 (EGR2) is a novel regulator of cellular senescence. This transcription factor activates key senescence pathways, offering a new marker for ageing and related diseases.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Gerontology

Background:

  • Cellular senescence, a stable growth arrest, is crucial in aging and age-related diseases.
  • The INK4/ARF locus is vital for senescence, but its transcriptional regulators are not fully understood.

Purpose of the Study:

  • To identify novel regulators of the p16/pRB and ARF/p53/p21 senescence pathways.
  • To investigate the role of EGR2 in cellular senescence.

Main Methods:

  • siRNA screening in deeply senescent human mammary epithelial cells (DS HMECs) and fibroblasts (DS HMFs).
  • Analysis of EGR2 expression, promoter binding, and effects on senescence markers.
  • EGR2 overexpression studies.

Main Results:

  • EGR2 was identified as a novel regulator of senescence, upregulated during the process.
  • EGR2 ablation transiently reversed the senescent phenotype in DS HMECs and HMFs.
  • EGR2 directly activates the ARF and p16 promoters, and its loss down-regulates p16.

Conclusions:

  • EGR2 is a direct transcriptional activator of the p16/pRB and ARF/p53/p21 pathways in senescence.
  • EGR2 functions as a novel marker and regulator of cellular senescence.

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