Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells

Elizabeth R. Smith, Kathy Qi Cai, Jennifer L. Smedberg, Melina M. Ribeiro, Malgorzata E. Rula, Carolyn Slater, Andrew K. Godwin, Xiang Xi Xu

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Background: The MAPK/ERK1/2 serine kinases are primary mediators of the Ras mitogenic signaling pathway. Phosphorylation by MEK activates MAPK/ERK in the cytoplasm, and phospho-ERK is thought to enter the nucleus readily to modulate transcription.Principal Findings:Here, however, we observe that in primary cultures of breast and ovarian epithelial cells, phosphorylation and activation of ERK1/2 are disassociated from nuclear translocalization and transcription of downstream targets, such as c-Fos, suggesting that nuclear translocation is limited in primary cells. Accordingly, in import assays in vitro, primary cells showed a lower import activity for ERK1/2 than cancer cells, in which activated MAPK readily translocated into the nucleus and activated c-Fos expression. Primary cells express lower levels of nuclear pore complex proteins and the nuclear transport factors, importin B1 and importin 7, which may explain the limiting ERK1/2 import found in primary cells. Additionally, reduction in expression of nucleoporin 153 by siRNA targeting reduced ERK1/2 nuclear activity in cancer cells. Conclusion: ERK1/2 activation is dissociated from nuclear entry, which is a rate limiting step in primary cells and in vivo, and the restriction of nuclear entry is disrupted in transformed cells by the increased expression of nuclear pores and/or nuclear transport factors.

Original languageEnglish (US)
Article numbere0009295
JournalPloS one
Volume5
Issue number2
DOIs
StatePublished - 2010

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Smith, E. R., Cai, K. Q., Smedberg, J. L., Ribeiro, M. M., Rula, M. E., Slater, C., Godwin, A. K., & Xu, X. X. (2010). Nuclear Entry of Activated MAPK Is Restricted in Primary Ovarian and Mammary Epithelial Cells. PloS one, 5(2), [e0009295]. https://doi.org/10.1371/journal.pone.0009295