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Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy

Alessandro Tubita1, Zoe Lombardi1, Ignazia Tusa1

  • 1Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.

International Journal of Molecular Sciences
|February 7, 2020
PubMed

Insights

Mitogen-activated protein kinases (MAPK) are crucial in diseases like cancer. Extracellular signal-regulated kinase 5 (ERK5) nuclear translocation is key for cancer progression and offers a potential therapeutic target.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • Mitogen-activated protein kinases (MAPK) signaling pathways are implicated in various human pathologies, including cancer and inflammatory disorders.
  • Aberrant MAPK signaling, particularly nuclear translocation, drives cancer onset and progression by regulating gene expression.

Purpose of the Study:

  • To review the mechanisms governing ERK5 (extracellular signal-regulated kinase 5) nucleo-cytoplasmic shuttling.
  • To explore the potential of targeting ERK5 trafficking for novel cancer therapeutics.

Main Methods:

  • Review of existing literature on ERK5 regulation and nuclear transport.
  • Analysis of post-translational modifications, chaperone interactions, and phosphorylation in ERK5 activity.
  • Examination of ERK5's role in gene expression and cellular proliferation.

Main Results:

  • ERK5, a larger MAPK, exhibits complex regulation through phosphorylation, post-translational modifications, and chaperone binding.
  • Multiple mechanisms control the nucleo-cytoplasmic shuttling of ERK5, highlighting its nuclear importance.
  • ERK5's nuclear translocation is a critical event in pro-proliferative signaling relevant to cancer.

Conclusions:

  • Understanding ERK5 trafficking mechanisms is crucial for its role in cancer.
  • Targeting ERK5 nuclear import/export pathways presents a promising strategy for developing new anti-cancer treatments.
Keywords:
BMK1MAPKMAPK7SUMOylationalternative kinase targetingchaperonesnuclear localizationnuclear signalingprotein phosphorylationubiquitination

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