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 neuro-degenerative 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 ex-traordinary pace with the recent progress in this area, the molecular mechanisms deter-mining whether a cell lives or dies are not fully understood. Phosphorylation and dephosphorylation of intracellular effector molecules are the most common and impor-tant 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 memberof the mitogen-activated protein (MAP) kinase kinase kinase family, which acti-vates both the SEK1-INK and MKK3/6-p38 MAP kinase pathways and constitutes a piv-otal 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.
The Japanese Biochemical Society