: Mutations or changes in normal cellular genes are generally linked to human cancer. Multiple gene changes involving at least two types of cancer genes, protooncogenes and tumor suppressor genes, are required for the clonal expansion of a malignant cell. The RIZ gene plays an important role in human cancer and more particularly in breast cancer. RIZ is the founding member of the PR-domain family of zinc finger genes. Two protein products. are produced from the RIZ gene which differ by the presence or the absence of the PR domain : RIZ1 and RIZ2. RIZ1 is commonly lost or under expressed in tumors whereas RIZ2 is always present. RIZ1 is a tumor suppressor whereas RIZ2 is not. In this project, we are trying to characterize the structural and the functional role of the RIZ1-PR and/or related domains using protein crystallography. Our goal is to understand the tumor-suppression mechanism of RIZ1 and PR-proteins in breast cancer. This will provide us new tools for possible treatment in breast cancer.

The yeast Saccharomyces cerevisiae F1F0-ATPase epsilon-subunit (61 residues) was synthesized by the solid-phase peptide approach under both acidic and basic strategies. Only the latter strategy allowed us to obtain a pure epsilon-subunit. The strong propensity of the protein to produce few soluble dimeric species depending on pH has been proved by size-exclusion chromatography, electrophoresis and mass spectrometry. A circular dichroism study showed that an aqueous solution containing 30% trifluoroethanol or 200 mM sodium dodecyl sulphate is required for helical folding. In both solvents at acidic pH, the epsilon-subunit is soluble and monomeric.