Bone Morphogenetic Proteins in the Initiation and Progression of Breast Cancer

Abstract

Due to their vast roles in human development, differentiation, homeostasis, and disease, bone morphogenetic proteins (BMP) have evolved along with numerous potentiating and inhibitory mechanisms to fine-tune signaling outcomes. As such, this chapter focuses on some of the best-studied and utilized extracellular mechanisms of BMP signal regulation. Due to their inherent binding characteristics, BMP ligands are often found engaged with at least of one of these many interacting partners. From a structural and functional perspective, we discuss our current understanding of how BMP ligands interact with these numerous binding partners, including secreted extracellular antagonists, BMP prodomains, and various co-receptors and noncanonical binding partners. Interestingly, while the BMP ligands themselves exhibit very redundant structural features, the composition and structure of their interacting proteins is quite diverse, lending to different ligand-binding modes and mechanisms, which lead to very different biological outcomes. Collectively, biochemical and structural characterization of these important interactions has provided valuable insight into BMP signal regulation.