Ubiquitin Ligases in Metabolism, Immune Checkpoint and Resistance to Therapy

The presentation will focus on the ubiquitin ligase RNF5 and its role in control of glutamine metabolism in breast cancer, and immune checkpoint and gut microbiome in melanoma. Our studies have demonstrated that RNF5 control the stability of glutamine carrier proteins, which in turn determine glutamine metabolism, mTOR signaling, autophagy, and susceptibility to cell death in breast cancer subjected to taxane therapy (Cancer Cell, 2015). The implications for stratifying breast cancer patients for select therapies will be discussed.  In more recent studies RNF5 was found to impact melanoma development, in part through its ability to orchestrate the control of immune checkpoint and gut microbiome.