| Transforming growth factor beta facilitates beta TrCP mediated degradation of Cdc25A in a Smad 3 dependent manner . ^^^ Here we demonstrate that the transforming growth factor beta ( TGF beta ) Smad 3 pathway promotes SCF ( beta TrCP ) mediated Cdc25A ubiquitination . ^^^ Cells treated with TGF beta , as well as cells transfected with Smad 3 or a constitutively active type 1 TGF beta receptor , exhibit increased ubiquitination and markedly shortened half lives of Cdc25A . ^^^ Furthermore , Cdc25A is stabilized in cells transfected with Smad 3 small interfering RNA ( siRNA ) and cells from Smad 3 null mice . ^^^ TGF beta induced ubiquitination is associated with Cdc25A phosphorylation at the beta TrCP docking site ( DS82G motif ) and physical association of Cdc25A with Smad 3 and beta TrCP . ^^^ |