METHODS FOR MODULATING BONE FORMATION AND MINERALIZATION BY MODULATING KRC ACTIVITY

摘要

This invention demonstrates that KRC molecules have multiple important functions as modulating agents in regulating a wide variety of cellular processes including bone formation and mineralization. TGF-ß signaling in osteoblasts promotes the formation of a multimeric complex between KRC, Runx2, Smad3, and the E3 ubiquitin ligase, WWPl which inhibits Runx2 function due to the ability of WWPl to promote Runx2 polyubiquitination and proteasome-dependent degradation. Furthermore, KRC and WWPl form a complex with RSK2 which promotes RSK2 phosphorylation and inhibits RSK2 function due to the ability of WWP 1 to promote RSK2 ubiquitination. Methods for identifying modulators of KRC activity are provided. Methods for modulating an immune response, bone formation and mineralization, and KRC-associated disorders using agents that modulate KRC expression and/or activity are also provided.