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Nuclear entry of activated MAPK is restricted in primary ovarian and mammary epithelial cells

Elizabeth R Smith1, Kathy Qi Cai, Jennifer L Smedberg

  • 1Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, United States of America. esmith@med.miami.edu

Plos One
|February 23, 2010
PubMed
Abstract

Insights

Nuclear entry of activated MAPK/ERK1/2 is limited in primary cells but readily occurs in cancer cells. This nuclear translocation is crucial for gene transcription and is regulated by nuclear pore proteins.

Area of Science:

  • Cellular Biology
  • Molecular Signaling
  • Cancer Research

Background:

  • Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) 1/2 are key serine kinases in the Ras signaling pathway.
  • MEK-mediated phosphorylation activates MAPK/ERK in the cytoplasm, facilitating nuclear entry for transcriptional modulation.

Purpose of the Study:

  • To investigate the nuclear translocation of activated MAPK/ERK1/2 in primary versus cancer cells.
  • To identify factors limiting ERK1/2 nuclear import in primary cells.

Main Methods:

  • In vitro import assays using primary and cancer cells.
  • Analysis of nuclear pore complex proteins and nuclear transport factors (importin B1, importin 7).
  • siRNA-mediated knockdown of nucleoporin 153.

Main Results:

  • Primary cells exhibit limited nuclear translocation of activated ERK1/2 compared to cancer cells.
  • Cancer cells show readily nuclear import of activated MAPK, leading to c-Fos expression.
  • Primary cells have lower expression of nuclear pore proteins and importins, potentially restricting ERK1/2 import.
  • siRNA targeting nucleoporin 153 reduced ERK1/2 nuclear activity in cancer cells.

Conclusions:

  • ERK1/2 activation is dissociated from nuclear entry in primary cells, representing a rate-limiting step.
  • Nuclear entry restriction is overcome in transformed cells due to increased expression of nuclear pores and/or transport factors.

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