Chapter Six - The Ubiquitin Network in the Control of EGFR Endocytosis and Signaling

Epidermal growth factor receptor (EGFR)-dependent signaling is involved in many physiological processes, and its deregulation leads to cellular dysfunctions and pathologies, of which cancer tops the list. Ubiquitin is the major determinant of EGFR fate all along the endocytic pathway, directly controlling EGFR signaling output. Indeed, the EGFR-ubiquitin network is often hijacked by cancer cells in order to have a proliferative advantage. In this chapter, we will review the different steps of EGFR activation and signal propagation, starting from the plasma membrane all the way down to the endosomal station, with a particular focus on the role of the ubiquitin system in controlling the balance between signal sustaining and downmodulation.