Grant: Operating Grant

The function of many proteins can be modulated by specific temporary modifications to their building blocks (amino acids). These reversible modifications are the basis for how cells can relay signals from outside the cell all the way to regulating gene expression. In these signaling cascades, modified amino acids are usually recognized by specific interaction domains, that serve to either relay and/or integrate the signals. The modular nature of these domains, and the flexibility of their binding properties, have likely facilitated the evolution of cellular regulatory pathways. My laboraroty is interested in understanding the physiological role of methylation, a protein modification that is slowly emerging as a novel regulator of many cellular processes. Consistent with a role in regulatory cascades, methylation can affect the way protein interact with other proteins, is reversible, and a module that specifically recognizes methylated amino acids, the Tudor domain, has recently been uncovered. Intringuingly, Tudor domains are often found in proteins implicated in processes related to ribonucleic acid (RNA). From these considerations and results obtained in our recent studies, we propose that Tudor domains will serve as molecular adaptors to integrate methylation regulatory signals, and relay this information to influence RNA-related events. In order to explore this model, we will focus on a recently discovered Tudor domain-containing protein, named TDRD3 and study how this proteins participates in the cellular responses that help to promote cell survival in the face of various stress conditions relevant to cancer.