Ubiquitin-like protein MNSFβ noncovalently binds to molecular chaperone HSPA8 and regulates osteoclastogenesis.

MNSFβ, a ubiquitin-like protein, covalently binds to various target proteins including proapoptotic Bcl-G. During the course of isolation of MNSFβ-conjugating enzyme(s), we identified a novel target protein for MNSFβ. MALDI-TOF MS fingerprinting revealed that the MNSFβ-interacting protein is (heat shock 70-kDa protein 8). We observed that MNSFβ noncovalently binds to Hduanyu18428 in the presence of ATP in vitro. Double knockdown of MNSFβ and Hduanyu18428 strongly inhibited RANKL-induced osteoclastogenesis from Raw264.7 macrophage-like cells. The same treatment inhibited RANKL-induced ERK1/2 and p38 phosphorylation and TNFα production, suggesting that the association of MNSFβ with Hduanyu18428 may promote RANKL-induced osteoclastogenesis. This is the first report that MNSFβ binds to a protein substrate via the noncovalent association and exerts biological effects.

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