2001 Fiscal Year Final Research Report Summary
Roles of the MST1-JNK pathway for cell death induction
| 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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| Keywords | MST1 / JNK / apoptosis / Bax / nuclear condensation |
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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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[Publications] Morishima, Y., Gotoh, Y., Barrett, T., Takano, H., Davis, R.J., Shirasaki, Y., Greenberg, M.E.: "β-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand"J. Neurosci.. 21. 7551-7560 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Masuyama, N., Oishi, K., Mori, Y., Ueno, T., Takahama, Y., Gotoh, Y.: "Akt Inhibits the Orphan Nuclear Receptor Nur77 and T cell Apoptosis"J. Biol. Chem.. 276. 32799-32805 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Fujishiro, M., Gotoh, Y., Katagiri, H., Sakoda, H., Ogihara, T., Anai, M., Onishi, Y., Ono, H., Funaki, M., Inukai, K., Fukushima, Y., Kikuchi, M., Oka, Y., Asano, T.: "MKK6/3 and p38 MAPK Pathway Activation is not Necessary for Insulin-Induced Glucose Uptake, but Regulates Glucose Transporter Expression"J. Biol. Chem.. 276. 19800-19806 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Morishima, Y., Gotoh, Y., Barrett, T., Takano, H., Davis, R. J., Shirasaki, Y. and Greenberg, M. E.: "(β-amyloid induces neuronal apoptosis via a mechanism that involves the c-Jun N-terminal kinase pathway and the induction of Fas ligand"J. Neurosci.. 21. 7551-7560 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Masuyama, N., Oishi, K., Mori, Y., Ueno, T., Takahama, Y. and Gotoh, Y.: "Akt Inhibits the Orphan Nuclear Receptor Nur77 and T cell Apoptosis"J. Biol. Chem.. 276. 32799-32805 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Fujishiro, M., Gotoh, Y., Katagiri, H., Sakoda, H., Ogihara, T., Anai, M., Onishi, Y., Ono, H., Funaki, M., Inukai, K., Fukushima, Y., Kikuchi, M., Oka, Y. and Asano, T.: "MKK6/3 and p38 MAPK Pathway Activation is not Necessary for Insulin-Induced Glucose Uptake, but Regulates Glucose Transporter Expression"J. Biol. Chem.. 276. 19800-19806 (2001)
Description
「研究成果報告書概要(欧文)」より
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