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Promyelocytic leukemia (PML) protein plays important roles in regulating cell adhesion, morphology, proliferation and

Mei Kuen Tang1, Yong Jia Liang, John Yeuk Hon Chan

  • 1Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, N.T., Hong Kong. florencetang@cuhk.edu.hk

Plos One
|April 5, 2013
PubMed

Insights

PML protein regulates cellular functions. Its absence in knockout cells alters protein expression, affecting cell adhesion, proliferation, and migration, with NDRG1 playing a key role in these changes.

Area of Science:

  • Cell Biology
  • Proteomics
  • Molecular Biology

Background:

  • PML protein is crucial for cellular homeostasis, forming PML nuclear bodies (PML-NBs) involved in various cellular functions.
  • Understanding the proteomic landscape of PML-deficient cells is essential for elucidating PML's regulatory roles.

Purpose of the Study:

  • To identify differentially expressed proteins in mouse embryonic fibroblasts (MEFs) lacking PML (PML(-/-)) compared to normal MEFs (PML(+/+)).
  • To investigate the functional consequences of PML deficiency on cellular behavior and signaling pathways.

Main Methods:

  • Comparative proteomics using two-dimensional electrophoresis (2-DE) and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
  • Analysis of protein expression profiles in PML(-/-) and PML(+/+) MEFs.
  • Functional assays including cell adhesion, proliferation, and migration.
  • Gene silencing of NDRG1 and assessment of its impact on PML expression and TGF-β1 signaling.

Main Results:

  • Nine proteins were down-regulated and ten were up-regulated in PML(-/-) MEFs.
  • PML(-/-) MEFs exhibited reduced adhesion, increased proliferation, and slower migration compared to PML(+/+) MEFs.
  • Silencing NDRG1 in PML(+/+) MEFs increased proliferation, inhibited PML expression, and impaired TGF-β1 signaling.

Conclusions:

  • PML deficiency significantly alters the proteome, impacting key cellular processes like adhesion, migration, and proliferation.
  • NDRG1 is identified as a critical mediator, where its down-regulation in PML(-/-) cells contributes to enhanced proliferation and potentially affects TGF-β1 signaling.

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