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Discovery of a Gatekeeper Residue in the C-Terminal Tail of the Extracellular Signal-Regulated Protein Kinase 5 (ERK5)
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Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy

Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, 50134 Florence, Italy
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Int. J. Mol. Sci. 2020, 21(3), 938; https://doi.org/10.3390/ijms21030938
Received: 27 December 2019 / Revised: 28 January 2020 / Accepted: 29 January 2020 / Published: 31 January 2020
(This article belongs to the Special Issue Targeting MAPK in Cancer)
The importance of mitogen-activated protein kinases (MAPK) in human pathology is underlined by the relevance of abnormalities of MAPK-related signaling pathways to a number of different diseases, including inflammatory disorders and cancer. One of the key events in MAPK signaling, especially with respect to pro-proliferative effects that are crucial for the onset and progression of cancer, is MAPK nuclear translocation and its role in the regulation of gene expression. The extracellular signal-regulated kinase 5 (ERK5) is the most recently discovered classical MAPK and it is emerging as a possible target for cancer treatment. The bigger size of ERK5 when compared to other MAPK enables multiple levels of regulation of its expression and activity. In particular, the phosphorylation of kinase domain and C-terminus, as well as post-translational modifications and chaperone binding, are involved in ERK5 regulation. Likewise, different mechanisms control ERK5 nucleo-cytoplasmic shuttling, underscoring the key role of ERK5 in the nuclear compartment. In this review, we will focus on the mechanisms involved in ERK5 trafficking between cytoplasm and nucleus, and discuss how these processes might be exploited to design new strategies for cancer treatment. View Full-Text
Keywords: nuclear localization; nuclear signaling; MAPK; BMK1; MAPK7; alternative kinase targeting; SUMOylation; protein phosphorylation; ubiquitination; chaperones nuclear localization; nuclear signaling; MAPK; BMK1; MAPK7; alternative kinase targeting; SUMOylation; protein phosphorylation; ubiquitination; chaperones
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Tubita, A.; Lombardi, Z.; Tusa, I.; Dello Sbarba, P.; Rovida, E. Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy. Int. J. Mol. Sci. 2020, 21, 938.

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