Ubiquitin-Mediated Regulation of Cell Death, Inflammation, and Defense of Homeostasis.

Cell death and inflammation are ancient processes of fundamental biological importance in both normal physiology and human disease pathologies. The recent observation that apoptosis regulatory components have dual roles in cell death and inflammation suggests that these proteins function, not primarily to kill, but to coordinate tissue repair and remodeling. This perspective unifies cell death components as positive regulators of tissue repair that replaces malfunctioning or damaged tissues and enhances the resilience of epithelia to insult. It is now recognized that cells that die by apoptosis do not do so silently, but release a variety of paracrine signals to communicate with their cellular environment to ensure tissue regeneration, and wound healing. Moreover, inflammatory signaling pathways, such as those emanating from the TNF receptor or Toll-related receptors, take part in cell competition to eliminate developmentally aberrant clones. Ubiquitylation has emerged as crucial mediator of signal transduction in cell death and inflammation. Here, we focus on recent advances on ubiquitin-mediated regulation of cell death and inflammation, and how this is used to regulate the defense of homeostasis.