Understanding MAPK Signaling Pathways in Apoptosis

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.

1-Cinnamoyltrichilinin from Melia azedarach Causes Apoptosis through the p38 MAPK Pathway in HL-60 Human Leukemia Cells

“…Apoptosis is mediated by the activation of mitogen-activated protein kinases (MAPKs), including p38 MAPK (p38), c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) [ 13 ]. To determine the type of MAPK signaling pathway involved in the apoptosis of HL-60 cells exposed to CT, we performed Western blotting for phosphorylated p38, JNK, and ERK in HL-60 cells.…”

“…MAPK proteins, key regulators of cellular proliferation, differentiation, and apoptosis, are activated by cytokines or extracellular stresses [ 13 ]. Upon stimulation, serine/threonine kinases are phosphorylated and regulate numerous substrates, leading to differential signal transduction, depending on the type of stimulus.…”

A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases

“…Activated MAPKs phosphorylate various proteins, including transcription factors, resulting in the promotion of inflammatory responses [ 195 ]. The MAPK signaling pathway is also vital in cellular growth, differentiation, survival, and death [ 196 ].…”

The Relationship Between Actin Cytoskeleton and Membrane Transporters in Cisplatin Resistance of Cancer Cells

“…In cisplatininduced apoptosis, the p53 transcriptional activity preceded the activation of p38 (Bragado et al, 2007). Since all MAPKs target and phosphorylate p53 at its different positions (Yue and López, 2020), on the other hand, MAPKs are an upstream signal of p53-mediated regulation. These results suggest that there might be the crosstalk between p53 and MAPKs in cisplatintriggered signaling pathways, resulting in positive feedback loops (see Figure 2).…”