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The nuclear translocation of ERK1/2 as an anticancer target

Author

Listed:
  • Alexander Plotnikov

    (The Weizmann Institute of Science)

  • Karen Flores

    (The Weizmann Institute of Science)

  • Galia Maik-Rachline

    (The Weizmann Institute of Science)

  • Eldar Zehorai

    (The Weizmann Institute of Science)

  • Einat Kapri-Pardes

    (The Weizmann Institute of Science)

  • Denise A. Berti

    (The Weizmann Institute of Science)

  • Tamar Hanoch

    (The Weizmann Institute of Science)

  • Michal J. Besser

    (The Ella Lemelbaum Institute for Melanoma, The Sheba Medical Center, Ramat Gan, Tel Aviv University)

  • Rony Seger

    (The Weizmann Institute of Science)

Abstract

A hallmark of the ERK1/2 functioning is their nuclear translocation, which is mainly required for the induction of proliferation. Activated ERK1/2 molecules that remain in the cytoplasm initiate other activities, including immediate feedback loops. Prevention of the nuclear translocation should therefore inhibit proliferation, without affecting cytoplasm-induced cellular processes. Here we present an NTS-derived myristoylated phosphomimetic peptide, which blocks the interaction of importin7 and ERK1/2, and consequently the nuclear translocation of the latter. In culture, the peptide induces apoptosis of melanoma cells inhibits the viability of other cancer cells, but has no effect on non-transformed, immortalized cells. It even inhibits the viability of PLX4032- and U0126-resistant melanoma cells. In xenograft models, the peptide inhibits several cancers, and acts much better than PLX4032 in preventing melanoma recurrence. This study provides a proof of concept for using the nuclear translocation of ERK1/2 as a drug target for the combat of various ERK1/2-related cancers.

Suggested Citation

  • Alexander Plotnikov & Karen Flores & Galia Maik-Rachline & Eldar Zehorai & Einat Kapri-Pardes & Denise A. Berti & Tamar Hanoch & Michal J. Besser & Rony Seger, 2015. "The nuclear translocation of ERK1/2 as an anticancer target," Nature Communications, Nature, vol. 6(1), pages 1-11, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7685
    DOI: 10.1038/ncomms7685
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