| Project/Area Number |
12480214
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
GOTOH Yukiko Institute of Molecular and Cellular Biosciences, The University of Tokyo, Associate Professor, 分子細胞生物学研究所, 助教授 (70252525)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,700,000 (Direct Cost: ¥14,700,000)
Fiscal Year 2001: ¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 2000: ¥9,100,000 (Direct Cost: ¥9,100,000)
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| Keywords | MST1 / JNK / apoptosis / Bax / nuclear condensation / MST / カスペース |
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| Research Abstract |
There are three points we would like to emphasize in this research. (1) It is well established that caspases are the key players in apoptosis, but it is still largely unknown how caspases modulate their substrates' functions in order to execute each apoptotic phenomenon. In this paper, we show that caspase-mediated cleavage of MST1 induces its nuclear translocation by separating it from an NES-containing domain, and that the nuclear translocation of MST1 facilitates nuclear condensation. This finding revealed a mechanism by which caspase-mediated cleavage converts its substrate (MST1) into a functional molecule (by nuclear localization) which contributes to an apoptotic event (chromatin condensation). (2) Some apoptotic signal messengers should translocate into the nucleus to induce nuclear apoptosis, since the integrity of nuclear membrane is apparently maintained when chromatin condensation begins to take place. Based on this study, we propose that MST1 represents one of these messengers which transduce apoptotic signals from cytoplasm to nucleus. (3) To our knowledge, MST1 is the first example that a protein translocates into the nucleus by removal of its own NES upon cleavage. Nuclear translocation by removal of NES is also a novel mechanism of regulating a kinase.
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