In vivo, these mutations disrupt homo-oligomerization, indicating that trimerization of Smad4 is a critical function in signaling that is targeted by tumorigenic mutations. Of particular interest is how the Smad4 forms a functional hetero-complex with Smad2 and why this particular complex forms only in response to ligand activation. We are now in the process of addressing these issues by crystallizing and determining the x-ray structure of the binary complex. This is thought to be necessary for the Smad proteins to exert their transcriptional activity. Other tumor suppressors.
Breast cancer is the most common form of malignant tumors affecting women throughout the world.
Recent investigation revealed that BRCA1 physically associates with Rad51, a DNA repair enzyme, and this interaction may be critical for its tumor-suppressing activity. We are interested in a structural characterization of this interaction. Structural basls of Smad2 recognition by the Smad anchor for receptor activation. A structural basis for mutational inactivation of the tumour suppressor Smad4. DNA unwinding induced by zinc finger protein binding.