Smad5: signaling roles in hematopoiesis and osteogenesis

SMAD5 belongs to the receptor-activated Smad that function as intracellular signal transducers for transforming growth factor-beta superfamily. SMAD5 protein is composed of N-terminal domain responsible for DNA-binding, C-terminal domain primarily required for protein-protein interaction, and the linker region containing motif essential for ubiquitinized degradation. Recent investigation reveals SMAD5 as a negative regulator of embryonic hematopoiesis in a haploinsufficiency fashion, helping to elucidate the cytogenetic mechanism, by which SMAD5 acts as leukemia suppressor. To date, osteogenesis governed by Smad5-mediated signals is delicately orchestrated by its comprehensive interactions with global osteogenesis regulator RUNX2, transcriptional repressor Rob and Smad-interacting protein 1. Further delineation of its roles in hematopoiesis and osteogenesis will undoubtedly provide valuable insights into leukemia therapy and tissue engineering.