Smad3: A protein in a pathway that helps prevent tumors. Smad3 is a player in a cellular network relay system called the transforming growth factor B (TGF-B) signaling cascade. TGF-B binds to receptors on the surface of blood cells that develop in bone marrow and activates a multi-protein cascade that relays these external signals into the nucleus of the cell. These signals typically slow the rate at which these blood cells proliferate. When this signal pathway is interrupted, TGF-B can no longer control cell proliferation, and this can lead to leukemia. Loss of the Smad3 protein is a key event in childhood T-cell leukemia. The gene for Smad3 is on chromosome 15 in region 15q21-q22.