| 摘要 |
This invention demonstrates that KRC molecules have multiple important fu nctions as modulating agents in regulating a wide variety of cellular proces ses including bone formation and mineralization. TGF-.beta. signaling in ost eoblasts promotes the formation of a multimeric complex between KRC, Runx2, Smad3, and the E3 ubiquitin ligase, WWPl which inhibits Runx2 function due t o the ability of WWPl to promote Runx2 polyubiquitination and proteasome-dep endent degradation. Furthermore, KRC and WWPl form a complex with RSK2 which inhibits RS K2 function due to the ability of WWPl to promote RSK2 ubiquiti nation. Methods for identifying modulators of KRC activity are provided. Met hods for modulating an immune response, bone formation and mineralization an d KRC-associated disorders using agents that modulate KRC expression and/or activity are also provided.
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