Methods are provided for identifying agents that modulate signaling mediated by transforming growth factor beta (TGF-.beta.) and members of the TGF-.beta. family, such as bone morphogenic protein (BMP). Such agents may be identified using screens that evaluate candidate agents for the ability to modulate Smad protein degradation. Agents identified as described herein may be used to augment or inhibit signaling mediated by one or more TGF-.beta. family members in a variety of cell types and for therapeutic purposes.