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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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G protein-coupled receptor kinase 4-induced cellular senescence and its senescence-associated gene expression

Pingping Xiao1, Xishi Huang2, Lanzhen Huang3

  • 1Cell Signaling Laboratory, Guilin Medical University, Guilin, Guangxi 541004, China; Graduate College, Guilin Medical University, Guilin, Guangxi 541004, China.

Experimental Cell Research
|September 16, 2017
PubMed

Insights

G protein-coupled receptor kinase 4 (GRK4) triggers a p53-independent cellular senescence. Ectopic GRK4 expression halts cell proliferation and induces G1/G0 arrest, increasing senescence markers.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cellular senescence is a state of irreversible cell cycle arrest.
  • G protein-coupled receptors (GPCRs) and their kinases (GRKs) regulate cell division.
  • The role of GRKs in cell proliferation and senescence is largely unknown.

Purpose of the Study:

  • To investigate the role of GRK4 in cellular proliferation and senescence.
  • To identify signaling pathways modulated by GRK4 during senescence.

Main Methods:

  • HEK293 cells expressing GRK4-GFP were isolated using fluorescence-activated cell sorting (FACS).
  • Cell cycle progression was analyzed.
  • Senescence-associated-β-galactosidase (SA-β-Gal) activity was measured.
  • Expression profiling of senescence-related genes was performed using qRT-PCR.
  • Protein levels of key regulators were validated by immunoblotting.

Main Results:

  • Ectopic GRK4 expression halted HEK293 cell proliferation, inducing G1/G0 phase arrest.
  • GRK4 expression significantly increased SA-β-Gal activity.
  • Expression profiling revealed significant changes in 17 senescence-related genes, including upregulation of p16INK4, p27KIP1, and MAPK14.
  • Immunoblotting confirmed increased levels of p16, p27, and MAPK14, with no detectable p53 or p21Waf1/Cip1.

Conclusions:

  • GRK4 has a novel function in inducing p53-independent cellular senescence.
  • GRK4-induced senescence involves a complex signaling network, including cell cycle inhibitors and MAPK pathways.
  • This study uncovers a new role for GRK4 in regulating cell fate and proliferation.
Keywords:
Cellular senescenceG protein-coupled receptor kinase 4Gene expression profilingp53-independent senescence

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