SIGNAL TRANSDUCTION UNIT
Our group is interested in the structural characterisation, mostly using X-Ray diffraction techniques, of the molecular mechanisms involved in cancer. We have approached this broad target by focusing on the interactions that proteins might establish with other cellular partners in selected processes. We pay relevant attention to the study of interactions in order to understand the molecular mechanisms in the cell leading to tumor progression. This information is being used in order to try to interfere with the molecular processes leading to anomalies or disease.
We use biophysical methods of detection and quantification of protein-protein interactions and develop functional tools trying to understand some biological aspects of genes involved in cell proliferation. The purpose of developing these functional tools is to validate hypothesis generated by the analysis of the structures resolved in the laboratory and also provide possible therapeutic agents designed against proliferating cells. In this sense, we have demonstrated that disruption of protein interactions mediated by phosphatase PP2A using cell penetrating peptides, can directly induce caspase-9 dependent apoptosis in chronic limphocitic leukemia B cells and breast cancer human xenograft models.
Functional and structural studies using a combination of molecular, cell biology and structural techniques are being performed in the laboratory in relation to cancer progression. Our previous efforts on the downregulation of the Epidermal Growth Factor Receptor (EGFR) have now been extended to the molecular mechanisms controlling eukaryotic gene expression. We have solved the structure of the first DRG/DFRP complex, which is involved in translation, and revealed that DRG proteins are multimodular factors with three additional domains apart from the GTPase. The factors required for DRG/DFRP complex polysome recruitment have also been determined.
We have recently been interested in the structural characterization of factors involved in the maturation of pre-ribosomal RNA. We have revealed the interaction details of two components of the PeBoW complex in Chaetomium, Erb1 and Ytm1 which are essential for eukaryotic ribosome biogenesis. The role played by their respective ß-propellers in the interaction has been established. We are now continuing the characterization of interaction areas between factors involved in this complex and energetically demanding process
We also aim to shed some light in the role of the complex in gene expression during activation of adult stem cells (http://trastem.ibv.csic.es/).
Figure: Detail of the Chaetomium Erb1/Ytm1 interacting surface.