Molecular mechanisms of the decision between life and death: regulation of apoptosis by apoptosis signal-regulating kinase 1.
Coordination and balance between cell survival and apoptosis is crucial for normal development and homeostasis of multicellular organisms. Defects in control of this balance may contribute to a variety of diseases including cancer, autoimmune and neurodegenerative conditions. Although a large number of pro- and anti-apoptotic factors acting for or against the final death event have been and are being discovered at an extraordinary pace with the recent progress in this area, the molecular mechanisms determining whether a cell lives or dies are not fully understood. Phosphorylation and dephosphorylation of intracellular effector molecules are the most common and important regulatory mechanisms in signal transduction and control a variety of cellular events from cell growth to apoptosis. Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein (MAP) kinase kinase kinase family, which activates both the SEK1-JNK and MKK3/6-p38 MAP kinase pathways and constitutes a pivotal signaling pathway in cytokine- and stress-induced apoptosis. This review provides recent findings on the molecular mechanisms which determine cell fate such as survival, proliferation, differentiation or apoptosis, with special focus on the regulatory mechanisms of ASK1-mediated apoptosis.
Matsuzawa
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A
Laboratory of Cell Signaling, Graduate School, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Ichijo
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H
D000818:Animals; D017209:Apoptosis; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008928:Mitochondria / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011485:Protein Binding; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D019014:fas Receptor / Q000378:metabolism
D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; D048848:MAP Kinase Kinase Kinase 5; D020930:MAP Kinase Kinase Kinases