Apoptosis Signal-Regulating Kinase 1 in Stress and Immune Response

Abstract

Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. ASK1 is preferentially activated by various cytotoxic stressors and plays pivotal roles in a wide variety of cellular response to them. Recent analyses of ASK1 orthologs in Caenorhabditis elegans and Drosophila melanogaster have revealed that ASK1 is an evolutionarily conserved signaling intermediate in stress responses and appears to constitute a primitive but efficient defense system against stimuli harmful to organisms. Consistent with this notion, ASK1 has been shown to be required for the innate immune response, which is essential for host defense against a wide range of pathogens. In this review, we focus on the molecular mechanisms by which ASK1 functions in stress and immune responses and discuss the possible involvement of ASK1 in human diseases.