Study of ric3 related to ICE with apoptosis-driving activity

细胞凋亡是一个重要的自杀程序，涉及多种生物现象，包括形态发生和组织稳态的维持。细胞凋亡是生物学和医学领域的一个重要课题，因为细胞凋亡的失调会导致多种疾病，如癌症和阿尔茨海默病。然而，细胞凋亡的分子基础在很大程度上仍然是未知的。我们一直在研究具有细胞凋亡驱动活性的ICE（白细胞介素1- β转换酶）家族蛋白酶。虽然在哺乳动物中已经发现了几个与ice相关的基因，但哪一个成员参与了细胞凋亡还有待确定。我们重点研究了与ICE相关的两个基因ric2和ric3，这两个基因与ICE本身的关系最为密切。我们使用显性阴性突变体和特异性抗体证明ric2参与fas介导的细胞凋亡，首次提供了ric2在凋亡细胞死亡中起重要作用的证据。我们还发现ric2和ric3基因产物的蛋白水解活性被CrmA抑制，CrmA最初被鉴定为ICE抑制剂，最近被证明可以抑制多种形式的细胞凋亡，这表明ric2和ric3在细胞凋亡中发挥重要作用。由于具有细胞凋亡诱导活性的元素可能对癌症的治疗非常有用，这些数据不仅有助于了解细胞凋亡的分子基础，而且有助于肿瘤疾病的控制。

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.