Regulation of TGF-β receptor degradation and expression. (a) TGF-β receptors localized in lipid raft/caveolae and caveolin-1-positive vesicles undergo ubiquitination. Smad7 recruits HECT domain-containing E3 ligases to mediate ubiquitination and degradation of TβRI. (b) TSC-22 competes with Smad7/Smurfs for TβRI binding and therefore decreases the ubiquitination and degradation of the receptor, leading to enhanced TGF-β signaling. PM: plasma membrane.