Defining specific protein interactions in Diaphanous-related Formins: an essential step in the development of a potential anti-cancer drug
Our project revolves around the Diaphanous-related formins (DRFs), which are a conserved family of proteins that act as "molecular switches" to play an important role in the regulation of cell shape, cell motility, and cell division. Since DRF proteins are an important focal point which can affect so many cellular processes, it is vital that DRFs are tightly regulated and only activated in response to a cellular signal, as uncontrolled DRFs can result in cell death. DRFs are multi-domain molecules that include a Diaphanous inhibitory domain (DID) that resides at one end of the protein and a Diaphanous autoregulatory domain (DAD) at the opposite end of the protein. In resting cells, DRFs are normally kept inactive by interactions between the DID and DAD domains until a specific "signal" activates the DRF. In cells, this signal is a class of proteins known as the small GTPases (such as Rho), which binds to the DID, triggering an "opening" and thus activation of the DRF. Since prolonged activation of the DRFs can cause cells to die, this led to the question: can this knowledge be used in a beneficial way to develop an anti-cancer drug? After testing over 10,000 different molecules for their ability to bind the DID region two compounds have been discovered that can bind to DID and subsequently has been shown to kill breast and colon cancer cells. The goal of this project is to characterize the DID-compound I/II binding site that is required to kill cancer cells.
Faculty Mentors: Greg Wolfe and Christian Trefftz, Computer Science
Page last modified July 14, 2009