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

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

Utilizing cellular and biochemical assays, key interactions and molecular roles for the RNF11 protein in the TGF-beta pathway were explored.

RESULTS:

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.

CONCLUSION:

RNF11 acts directly on Smad4 to enhance Smad4 function, and plays a role in prolonged TGF-beta signalling and possibly in latent tumour progression.

• Authors: Peter B Azmi, Arun K Seth
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 6 Pg. 2253-63 (Jun 2009) ISSN: 0250-7005 [Print] Greece
• PMID: 19528490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carrier Proteins
• DNA-Binding Proteins
• RNF11 protein, human
• SMAD4 protein, human
• Smad4 Protein
• Transforming Growth Factor beta
• Ubiquitin

Topics

• Apoptosis
• Blotting, Western
• Breast Neoplasms (genetics, metabolism, pathology)
• Carcinoma, Hepatocellular (genetics, metabolism, pathology)
• Carrier Proteins (genetics, metabolism)
• Cells, Cultured
• DNA-Binding Proteins
• Fluorescent Antibody Technique
• Humans
• Immunoblotting
• Immunoprecipitation
• Kidney (metabolism, pathology)
• Liver Neoplasms (genetics, metabolism, pathology)
• Signal Transduction
• Smad4 Protein (genetics, metabolism)
• Transforming Growth Factor beta (genetics, metabolism)
• Ubiquitin (metabolism)