| NEDD 4 2 ( neural precursor cell expressed , developmentally down regulated 4 2 ) negatively regulates TGF beta ( transforming growth factor beta ) signalling by inducing ubiquitin mediated degradation of Smad 2 and TGF beta type 1 receptor . ^^^ Moreover , NEDD 4 2 bound to TGF beta specific R Smads , Smads 2 and 3 , in a ligand dependent manner , and induced degradation of Smad 2 , but not Smad 3 . ^^^ However , in contrast with Smurf 2 , NEDD 4 2 failed to induce ubiquitination of SnoN ( Ski related novel protein N ) , although NEDD 4 2 bound to SnoN via Smad 2 more strongly than Smurf 2 . ^^^ |