Multiple myeloma cells are often resistant to many forms of therapy. Our laboratory has shown that a protein called Mcl-1 helps to keep MM cells alive; blocking Mcl-1 production induces the rapid death of MM cells through a process called apoptosis. In this proposal, we will analyze the mechanisms through which Mcl-1 protects the MM cells from apoptosis. By studying the molecular interactions between Mcl-1 and other cellular proteins that are known to trigger cell death, we will be able to generate a model of Mcl-1 function. The scientific knowledge gained from these experiments will be used to develop an experimental system to identify small molecule inhibitors of Mcl-1 that will have the potential of becoming potent anti-myeloma drugs.