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Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
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Serum response factor controls CYLD expression via MAPK signaling pathway

Gang Liang1, Kristofer Ahlqvist, Rajeswararao Pannem

  • 1Department of Laboratory Medicine, Lund University, UMAS, Malmö, Sweden.

Plos One
|May 17, 2011
PubMed

Insights

Loss of the tumor suppressor CYLD increases cell proliferation. Serum response factor (SRF) and p38 MAPK regulate CYLD expression, preventing excessive cell growth in MEF cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The CYLD gene functions as a tumor suppressor by deubiquitinating key signaling molecules.
  • Loss of CYLD is implicated in tumor development, affecting cell survival and proliferation.

Purpose of the Study:

  • To investigate the role of CYLD in mouse embryonic fibroblast (MEF) proliferation.
  • To elucidate the molecular mechanisms regulating CYLD expression in response to serum stimulation.

Main Methods:

  • Comparison of proliferation rates between CYLD-/- and CYLD+/+ MEFs.
  • Analysis of serum response factor (SRF) binding to the CYLD promoter.
  • Assessment of p38 mitogen-activated protein kinase (MAPK) involvement.
  • Use of siRNA to deplete SRF and pharmacological inhibitors for p38 MAPK.

Main Results:

  • CYLD-/- MEFs exhibit increased proliferation compared to CYLD+/+ MEFs in a serum-dependent manner.
  • Serum stimulation upregulates CYLD expression in CYLD+/+ MEFs via SRF binding to the CYLD promoter.
  • p38 MAPK activity is essential for SRF recruitment to the CYLD promoter.
  • SRF depletion or p38 MAPK inhibition reduces CYLD levels and enhances MEF proliferation.

Conclusions:

  • SRF acts as a positive regulator of CYLD expression.
  • CYLD negatively regulates serum-induced proliferation in MEF cells.
  • The SRF-p38 MAPK pathway controls CYLD expression to limit aberrant cell proliferation.

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