Multiple roles of mothers against decapentaplegic homolog 4 in tumorigenesis, stem cells, drug resistance, and cancer therapy

Figure 1 Structure and features of mothers against decapentaplegic homolog 4. A: Location of the mothers against decapentaplegic homolog 4 (Smad4) gene. Smad4 is located at q21.1 of human chromosome 18; B: Structural diagram of Smad4 protein. Smad4 protein consists of three domains: Mad homology domain 1 (MH1) at the N-terminal, MH2 at the C-terminal, and the linker region connecting MH1 and MH2. Functionally, MH1 is responsible for binding to the Smad-binding site, and MH2 is indispensable for transforming growth factor-β transcriptional activity. The middle linker is rich in regulatory sites controlling various signaling pathways and kinases and is essential for the regulation of transcriptional activity. MH1: Mad homology domain 1; MH2: Mad homology domain 2; NES: Nuclear export signal; SAD: Smad activation domain; Smad4: Mothers against decapentaplegic homolog 4.