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      Understanding MAPK Signaling Pathways in Apoptosis

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          Abstract

          MAPK (mitogen-activated protein kinase) signaling pathways regulate a variety of biological processes through multiple cellular mechanisms. In most of these processes, such as apoptosis, MAPKs have a dual role since they can act as activators or inhibitors, depending on the cell type and the stimulus. In this review, we present the main pro- and anti-apoptotic mechanisms regulated by MAPKs, as well as the crosstalk observed between some MAPKs. We also describe the basic signaling properties of MAPKs (ultrasensitivity, hysteresis, digital response), and the presence of different positive feedback loops in apoptosis. We provide a simple guide to predict MAPKs’ behavior, based on the intensity and duration of the stimulus. Finally, we consider the role of MAPKs in osmostress-induced apoptosis by using Xenopus oocytes as a cell model. As we will see, apoptosis is plagued with multiple positive feedback loops. We hope this review will help to understand how MAPK signaling pathways engage irreversible cellular decisions.

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          Most cited references129

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          AP-1: a double-edged sword in tumorigenesis.

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            JNK signaling in apoptosis.

            Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.
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              p38 MAP-kinases pathway regulation, function and role in human diseases.

              Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines. There are four members of the p38MAPK family (p38alpha, p38beta, p38gamma and p38delta) which are about 60% identical in their amino acid sequence but differ in their expression patterns, substrate specificities and sensitivities to chemical inhibitors such as SB203580. A large body of evidences indicates that p38MAPK activity is critical for normal immune and inflammatory response. The p38MAPK pathway is a key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of this pathway potential targets for the treatment of autoimmune and inflammatory diseases. However, recent studies have shed light on the broad effect of p38MAPK activation in the control of many other aspects of the physiology of the cell, such as control of cell cycle or cytoskeleton remodelling. Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies.

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                28 March 2020
                April 2020
                : 21
                : 7
                : 2346
                Affiliations
                [1 ]School of Biology and Basic Medical Sciences, Soochow University Medical College, 199 Ren’ai Road, Suzhou 215123, China; jicheng_yue@ 123456suda.edu.cn
                [2 ]Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
                Author notes
                [* ]Correspondence: josemanuel.lopez@ 123456uab.cat ; Tel.: +34-935-814-278
                Article
                ijms-21-02346
                10.3390/ijms21072346
                7177758
                32231094
                f9b2039f-3163-4c16-b8c2-5313ab113957
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 February 2020
                : 25 March 2020
                Categories
                Review

                Molecular biology
                apoptosis,protein kinases,caspases,signaling,mapk,p38,jnk,erk,oocytes,feedback loops
                Molecular biology
                apoptosis, protein kinases, caspases, signaling, mapk, p38, jnk, erk, oocytes, feedback loops

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