Molecular Mechanism of Apoptosis Signal Regulating Kinase-1 Oligomerization and Auto-activation

Abstract

Apoptosis signal regulating kinase 1 (ASK1) is one of the most important enzymes of MAPK pathway which is involved in mediating diverse signal leading to cell death, differentiation, survival and senescence. ASK1 is a crucial element of stress and cytokine induced apoptosis. The growing interest in research on ASK1 is due to its abnormal regulation in various diseases such as cancers, cardiovascular diseases, neurodegenerative disorders, inflammatory diseases and diabetes. As a result, this signal transducing protein has become a popular therapeutic target in treating these diseases in order to provide less toxic pharmaceutical treatment options. In this regard, it is very important to understand the detailed mechanism of ASK 1 activation to elucidate the molecular mechanisms of ASK1-initiated signal transduction. We intend to explore the structural and functional basis of ASK1 activation by understanding the self-assembling oligomerization of ASK1 by a combination of mutagenesis, protein-protein interaction assays, and kinetic analysis.