The RING finger protein11 binds to Smad4 and enhances Smad4-dependant TGF-beta signalling.

In breast carcinomas, prolonged signalling through the TGF-beta receptor promotes latent tumour progression, metastasis and the epithelial-to-mesenchymal transition of tumour cells. Previously, it has been found that the 154 amino acid RING finger protein, RNF11, was overexpressed in high-grade breast tumours and was capable of modulating TGF-beta signalling.,Utilizing cellular and biochemical assays, key interactions and molecular roles for the RNF11 protein in the TGF-beta pathway were explored.,It is shown that RNF11 is required for TGF-beta signalling and is capable of enhancing the Smad-TGF-beta signalling pathway directly. Further, that endogenous RNF11 and Smad4 proteins associate and co-localize in a TGF-beta-enhanced manner. This study indicates that RNF11 induces an increase in Smad4 protein levels. In functional assays, it is observed that RNF11 enhances Smad4-dependant TGF-beta signalling and that RNF11 alone can recapitulate Smad4-dependant apoptosis in cellular assays.,RNF11 acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signalling and possibly in latent tumour progression.