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.

Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy / Tubita, Alessandro; Lombardi, Zoe; Tusa, Ignazia; Dello Sbarba, Persio; Rovida, Elisabetta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - ELETTRONICO. - 21:(2020), pp. 938-954. [10.3390/ijms21030938]

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

Tubita, Alessandro
Writing – Original Draft Preparation
;
Lombardi, Zoe
Writing – Original Draft Preparation
;
Tusa, Ignazia
Writing – Review & Editing
;
Dello Sbarba, Persio
Writing – Review & Editing
;
Rovida, Elisabetta
Conceptualization
2020

Abstract

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.
2020
21
938
954
Goal 3: Good health and well-being for people
Tubita, Alessandro; Lombardi, Zoe; Tusa, Ignazia; Dello Sbarba, Persio; Rovida, Elisabetta
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1183942
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