title: Ubiquitin-like protein MNSFβ noncovalently binds to molecular chaperone HSPA8 and regulates osteoclastogenesis.
abstract: 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 HSPA8 (heat shock 70-kDa protein 8). We observed that MNSFβ noncovalently binds to HSPA8 in the presence of ATP in vitro. Double knockdown of MNSFβ and HSPA8 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 HSPA8 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.
authors: The Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, 693-8501, Japan.
authors: Kaori
authors: K
authors: Notsu
authors: The Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, 693-8501, Japan.
authors: Mai
authors: M
authors: Nakagawa
authors: The Department of Cooperative Medical Research, Collaboration Center, Shimane University, Izumo, 693-8501, Japan. nkmr0515@med.shimane-u.ac.jp.
authors: Morihiko
authors: M
authors: Nakamura
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D050883:HSC70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism*; D011485:Protein Binding; D053245:RANK Ligand / Q000378:metabolism; D013491:Suppressor Factors, Immunologic / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050883:HSC70 Heat-Shock Proteins; C494372:Hspa8 protein, mouse; D053245:RANK Ligand; D013491:Suppressor Factors, Immunologic; C505689:Tnfsf11 protein, mouse; C072169:monoclonal nonspecific suppressor factor; D000255:Adenosine Triphosphate; D048052:Mitogen-Activated Protein Kinase 3
keywords: Heat shock cognate protein; Molecular chaperone; Osteoclastogenesis; RANKL; Ubiquitin-like protein