Specific Functions of the Farnesylation Modification of YDJ1 in Activation of HSP90 Client Proteins
In normal cells, a diverse array of proteins controls cell division. When the proteins that signal cells to divide become overly active, uncontrolled cellular growth occurs, and this may lead to development of cancer. Over the years researchers have identified many of the proteins that become overly active in different types of cancers. Although these proteins are expressed in different tissues and cause different types of cancer, many of the proteins have one thing in common: they require the activity of the molecular chaperone Hsp90 for function. As evidence for the importance of Hsp90 in promoting cancerous growth, inhibitors of Hsp90 have been found to limit the growth of different types of cancer and current clinical trials focus on the use of Hsp90 inhibitors as treatments for breast cancer, leukemias and multiple myeloma. Our research is
focused on trying to figure out how Hsp90 interacts with different types of proteins, called client proteins, and how the functions of Hsp90 change as cells respond to extracellular signals or metabolic states depending on the growth state of the cell. Hsp90 is an essential, abundant protein that regulates the function of many proteins involved in signaling pathways and control of cell division. Hsp90 interacts with a number of partner proteins, or co-chaperones, that are required for Hsp90 function. One possibility for the presence of these co-chaperones is that only some of them interact with client proteins involved in cancer, while others are involved in different functions of Hsp90. We are studying the specific roles of the co-chaperone Ydj1 in activation of Hsp90 client proteins. These studies will provide additional clues about how Hsp90 function helps cells survive and adapt to a
variety of environmental stresses common to tumor cells. Ultimately we hope to translate this knowledge into new strategies for inhibiting cancerous growth without harming non-cancerous cells.