Study of ric3 related to ICE with apoptosis-driving activity

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Apoptosis is an important suicide program involved in a variety of biological phenomena including morphogenesis and maintenance of tissue homeostasis. Apoptosis is an important theme not only in biology but also in medical field because dysregulation of apoptosis leads to various diseases such as cancer and Alzheimer's disease. However the molecular basis of apoptosis is still largely unknown. We have been studying ICE (interleukin 1-beta-converting enzyme) family proteases with apoptosis-driving activity. Although several ICE-related genes have been identified in mammals, it is still to be determined which member is involved in apoptosis.We focused on two ICE-related genes, ric2 and ric3, both of which are most closely related to ICE itself. We have shown using a dominant negative mutant and specific antibodies that ric2 is involved in Fas-mediated apoptosis, providing the first evidence for an essential role of ric2 in apoptotic cell death. We have also shown that proteolytic activity of ric2 and ric3 gene products are inhibited by CrmA which is initially identified as an ICE inhibitor and has recently been shown to inhibit many forms of apoptosis, suggesting that both ric2 and ric3 play an important role in apoptosis.Since elements with apoptosis-inducing scitivity might be very useful for treatment of cancers, these date would be useful not only for understanding molecular basis of apoptosis but also for control of neoplastic diseases.