Homeodomain-Interacting Protein Kinases: Diverse and Complex Roles in Development and Disease

The Homeodomain-interacting protein kinase (Hipk) family of proteins plays diverse, and at times conflicting, biological roles in normal development and disease. In this review we will highlight developmental and cellular roles for Hipk proteins, with an emphasis on the pleiotropic and essential physiological roles revealed through genetic studies. We discuss the myriad ways of regulating Hipk protein function, and how these may contribute to the diverse cellular roles. Furthermore we will describe the context-specific activities of Hipk family members in diseases such as cancer and fibrosis, including seemingly contradictory tumor-suppressive and oncogenic activities. Given the diverse signaling pathways regulated by Hipk proteins, it is likely that Hipks act to fine-tune signaling and may mediate cross talk in certain contexts. Such regulation is emerging as vital for development and in disease.