| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
MNSF, a ubiquitin-like protein, covalently binds to various target proteins including proapoptotic Bcl-G. During the course of isolation of MNSF-conjugating
enzyme(s), we identified a novel target protein for MNSF. MALDI-TOF MS fingerprinting revealed that the MNSF interacting protein is HSPA8 (heat shock 70-kDa protein 8). We observed that MNSF noncovalently binds to HSPA8 in the presence of ATP in vitro. Double knockdown of MNSF and HSPA8 strongly inhibited RANKL induced osteoclastogenesis from Raw264.7 macrophage-like cells. The same treatment inhibited RANKL-inducedERK1/2 and p38 phosphorylation and TNF production,suggesting that the association of MNSF with HSPA8 may promote RANKL-induced osteoclastogenesis. This is the first report that MNSF binds to a protein substrate via the noncovalent association and exerts biological effects.
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