| Budget Amount *help |
¥23,790,000 (Direct Cost: ¥18,300,000、Indirect Cost: ¥5,490,000)
Fiscal Year 2010: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2008: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
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| Research Abstract |
The abnormality of checkpoint and cell division during cell cycle is thought to be a trigger of carcinogenesis. APC/C ubiquitin ligase complex regulates the protein level of many key molecules for cell division. Emi1, an inhibitor of APC/C, inhibits APC/C activity from S phase to the beginning of M phase. In the present study, we found that APC/C inhibitor, Emi1 was frequently overexpressed in cancer cell lines and head and neck cancer cases. Moreover, we found a cancer cell line that constitutively expressed Emi1 during cell cycle progression. In this cell line, Ser310 and Thr315 of Emi1 were phosphorylated by ERK-RSK pathway and this phosphorylation inhibited ubiquitin-mediated proteolysis. Constitutive Emi1 expression inhibited APC/C activity during cell cycle progression and induced overexpression of APC/C substrates.In summary, Emi1 overexpression caused by the defects of degradation induced the constitutive inhibition of APC/C activity and was involved in abnormal regulation of cell cycle and carcinogenesis.
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