The MAPK cascades: signaling components, nuclear roles and mechanisms of nuclear translocation.

By A. Plotnikov, E. Zehorai, S. Procaccia, R. Seger. Biochimica et Biophysica Acta, 2011

955 citations recorded by the source corpus.

The MAPK cascades are central signaling pathways that regulate a wide variety of stimulated cellular processes, including proliferation, differentiation, apoptosis and stress response. Therefore, dysregulation, or improper functioning of these cascades, is involved in the induction and progression of diseases such as cancer, diabetes, autoimmune diseases, and developmental abnormalities. Many of these physiological, and pathological functions are mediated by MAPK-dependent transcription of various regulatory genes. In order to induce transcription and the consequent functions, the signals transmitted via the cascades need to enter the nucleus, where they may modulate the activity of transcription factors and chromatin remodeling enzymes. In this review, we briefly cover the composition of the MAPK cascades, as well as their physiological and pathological functions. We describe, in more detail, many of the important nuclear activities of the MAPK cascades, and we elaborate on the mechanisms of ERK1/2 translocation into the nucleus, including the identification of their nuclear translocation sequence (NTS) binding to the shuttling protein importin7. Overall, the nuclear translocation of signaling components may emerge as an important regulatory layer in the induction of cellular processes, and therefore, may serve as targets for therapeutic intervention in signaling-related diseases such as cancer and diabetes. This article is part of a Special Issue entitled: Regulation of Signaling and Cellular Fate through Modulation of Nuclear Protein Import.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/fc72deb165a158e263281421174b615d3da42abb

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

1. R. Roskoski

In Molecular Biology

1. Tomislav Domazet-Lošo
2. Ruibang Luo
3. Shan Wang
4. Yingrui Li
5. Ximing Guo
6. R. Roskoski

Citations in the corpus

• ERK/MAPK signalling pathway and tumorigenesis (2020, methodology): “Each MAPK signalling cascade consists of at least three tiers: MAP3K, MAPKK and MAPK (3,6) (Fig.”
• Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution (2024, background): “, MAPKs themselves can generate ROS as part of their signaling It has been estimated that oxidative stress can induce approximately 10,000 alterations in DNA per cell per day, encompassing various types of DNA damage.”
• A Comprehensive Review on MAPK: A Promising Therapeutic Target in Cancer (2019, background): “As previously mentioned, the MAPK pathways are an extensive regulatory network consisting of a series of crosstalking and compensatory pathways implicated in transducing distress, thereby affecting growth signals and cellular metabolism [8].”
• ROS and ROS-Mediated Cellular Signaling (2016, background): “Activated Raf phosphorylates MEK1/2 (MAPKK), which then phosphorylates ERK1/2 (MAPK) that translocate to the nucleus and activates several transcription factors [54, 55].”
• The Kinome of Pacific Oyster Crassostrea gigas, Its Expression during Development and in Response to Environmental Factors (2016, positive): “In various species including the gastropod Haliotis asinina, CMGC kinases including MAPK signaling are crucial in patterning and establishing axial symmetry during embryogenesis [102].”
• ERK1/2 MAP kinases: structure, function, and regulation. (2012, background): “[8].”