Regulation of Tumor Suppressor Par-4 by Ceramide

Prostate apoptosis response-4 (Par-4) is a pro-apoptotic protein that selectively induces apoptosis in cancer cells, thereby exerting prominent tumor-suppressing functions. Ceramides are important bioactive lipids belonging to the sphingolipid family. Both Par-4 and ceramide are critical regulators of cellular responses to acute stressors and has been clearly established as a key player in the execution of cell death. Though Par-4 and ceramide act as an apparent collaborator of cell-fate decisions, the relationship between these molecules is very complex, and mechanisms underlying their regulation are diverse and not fully characterized. In this chapter, we portray the role and mechanisms of action of Par-4 and ceramide in apoptosis and autophagy. Specifically, we are elaborating on the central role of Par-4 in ceramide-induced cell death signaling. Understanding the Par-4-ceramide connection will not only have profound importance to the understanding of programmed cell death pathways, but also will have an impact on interventions of cancer therapy and prevention.