TI - Direct interaction between Smad3 , APC10 , CDH1 and HEF1 in proteasomal degradation of HEF1 . AB - Background The Transforming Growth Factor-beta ( TGF-beta ) regulates myriad cellular events by signaling through members of the Smad family signal transducers . As a key signal transducer of TGF-beta , Smad3 exhibits the property of receptor -activated transcriptional modulator and also the novel ability of regulating the proteasomal degradation of two Smad3 interacting proteins , SnoN and HEF1 . It has been shown that Smad3 recruits two types of Ub E3 ligases , Smurf2 and the Anaphase Promoting Complex ( APC ) , to mediate SnoN ubiquitination , thereby enhancing SnoN degradation . The molecular mechanisms underlying Smad3 -regulated HEF1 degradation are not well understood . Furthermore , it is not clear how Smad3 recruits the APC complex . Results We detected physical interaction between Smad3 and an APC component APC10 , as well as the interaction between HEF1 and CDH1 , which is the SUBstrate -interacting component within APC . Detailed domain mapping studies revealed distinct subdomains within the MH2 domain of Smad3 for binding to APC10 and HEF1 and suggests the formation of a complex of these four proteins ( Smad3 , HEF1 , APC10 and CDH1 ) . In addition , the protein levels of HEF1 are subjected to the regulation of overexpressed APC10 and CDH1 . Conclusions Our data suggests that Smad3 may recruit the APC complex via a direct interaction with the APC subunit APC10 to regulate the ubiquitination and degradation of its interactor HEF1 , which is recognized as an ubiquitination SUBstrate by the CDH1 subunit of the APC complex .