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.
Liu
Bing
B
Department of Cell Biology, Institute of Basic Medical Sciences, Beijing, PR China.
Mao
Ning
N
D052004:Bone Morphogenetic Protein Receptors; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D010012:Osteogenesis / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051902:Smad5 Protein; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*
D004268:DNA-Binding Proteins; D010750:Phosphoproteins; D017978:Receptors, Growth Factor; C497797:SMAD5 protein, human; D051902:Smad5 Protein; D015534:Trans-Activators; D052004:Bone Morphogenetic Protein Receptors