Smad Transcription Factors
Mothers against decapentaplegic homolog (Smad) transcription factors are downstream effectors for TGF-beta signaling. Smads are divided into three groups based on function: Receptor-regulated (R)-Smads (1,2,3,5,8), common partner (Co)-Smad (4), and inhibitory (I)-Smads (6,7). R-Smads and Smad4 share highly conserved Mad Homology (MH)1 and MH2 domains. The MH1 domain is required for DNA binding to Smad-binding elements (SBEs). Smad3-Smad4 binds (5'-AGAC-3') and Smad1 binds (5'-G(A/G)CGNC-3'). Smad proteins only bind to SBEs with low affinity; interaction with other DNA-binding factors is frequently required for full Smad recruitment to DNA. The MH2 domain is required for these protein-protein interactions. Phosphorylation of R-Smads promotes the formation of homomeric complexes in addition to their interaction with Smad4. I-Smad proteins have the MH2 domain only and function to inhibit Smad signal transduction. Overall, Smad transcription factors regulate diverse functional responses in embryos and adult organisms.