Regulation of the Hippo signaling pathway by deubiquitinating enzymes in cancer

Regulation of the Hippo signaling pathway is essential for normal organ growth and tissue homeostasis. The proteins that act to regulate this pathway are important for ensuring proper function and cellular location. Deubiquitinases (DUBs) are a family of proteases that act upon many proteins. While ubiquitinases add ubiquitin and target proteins for degradation, DUBs act by removing ubiquitin (Ub) moieties. Changes in ubiquitin chain topology results in the stabilization of proteins, membrane trafficking, and the alteration of cellular localization. While the roles of these proteins have been well established in a cancer setting, their convergence in cancer is still under investigation. In this review, we discuss the roles that DUBs play in the regulation of the Hippo signaling pathway for homeostasis and disease.