Aurora2 protein regulated by the anaphase-promoting complex-ubiquitin-proteasome pathway.

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671214
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: 福井医科大学
• Principal Investigator: ISHIDA Makoto Fukui Medical University, First Department of Surgery, Assistant, 医学部, 教授 (10174608)
• Co-Investigator(Kenkyū-buntansha): 石田 誠 福井医科大学, 医学部, 助手 (00311689)
• Project Period (FY): 2000 – 2001
• Keywords: Aurora2 / gl-rine / threonine protein / ubiquitination / APC-ubiquitin-proteasome pathway

Research Abstract

Human Aurora2 was originally identified by its close homology to yeast IPL1 and fly aurora, which are key regulators of chromosome segregation and a cell cycle regulated serine/threonine protein kinase which is overexpressed in many tumor cell lines. We analyzed 100 colorectal cancer specimens for the expresssion of Aurora2 gene. The overexpression of Aurora2 gene was 62 % in primary colorectal cancers. Furthermore, we demonstrated that the Aurora2 protein is degraded rapidly after G2/M phase release in mammalian cells, (a half-life of approximately 2 h). The treatment of the cells with proteasome inhibitors blocks Aurora2 degradation. Aurora2 is polyubiquitinated in vivo and in vitro using anaphase-promoting complex (APC). These results demonstrate that Aurora2 protein js turned over through the APC-ubiquitin-proteasome pathway.
We hope that the regulation of APC-ubiquitin-proteasome pathway may be useful for tumor dormancy therapy.