Cornell University

Harvard College

Marc Wein

Laurie H Glimcher

Dallas C Jones

This invention is based, at least in part, on the discovery that Shn2 and Shn3 play an important role in skeletal remodeling and skeletal patterning. Accordingly, the present invention provides methods for identifying medulators of Shn2 activity and methods for modulating bone formation and mineralization and Shn2-associated disorders using agents that modulate Shn2 expression and/or activity, in addition to methods for modulating Shn2 and Shn3.

Methods for modulating skeletal remodeling and patterning by modulating SHN2 activity, SHN3 activity, or SHN2 and SHN3 activity in combination

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-&#x3b2; signaling in osteoblasts promotes the formation of a multimeric complex between KRC, Runx2, Smad3, and the E3 ubiquitin ligase, WWP1 which inhibits Runx2 function due to the ability of WWP1 to promote Runx2 polyubiquitination and proteasome-dependent degradation. Furthermore, KRC and WWP1 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.

Growing community of inventors

Brookline, MA, United States of America

Marc Wein