Regulation of Smad activities

TGF-β (Transforming Growth Factor-β) cytokines employ Smad proteins as the intracellular mediator of signaling. Upon TGF-β stimulation, the cytoplasmic Smads become phosphorylated and consequently accumulate in the nucleus to regulate target gene expression. The cytoplasm-to-nucleus redistribution of Smads, as well as the ability of Smads to activate or repress gene transcription, is under multiple layers of regulation by factors not limited to TGF-β. With recent advance in the knowledge of regulatory factors impinged on Smads, we are beginning to understand the complexity in cellular responses to TGF-β.