Description_x000D_ General description_x000D_ SMAD4 is a member of the SMAD family and mediates signaling by the transforming growth factor-beta (TGFβ) superfamily and related ligands. TGFβ stimulation leads to phosphorylation and activation of SMAD1, SMAD2 and SMAD3, which form complexes with SMAD4 that accumulate in the nucleus and regulate transcription of target genes. SMAD signaling is negatively regulated by inhibitory SMADs and ubiquitin-mediated processes and proteasomal degradation of SMADs depend on the direct interaction of specific E3 ligases with SMADs. SMAD4 is targeted for degradation by multiple ubiquitin ligases that can simultaneously act on R-SMADs and signaling receptors. Such mechanisms of down-regulation of TGFβ signaling via degradation of SMADs may be critical for proper physiological response to this pathway._x000D_ Physical form_x000D_ Supplied in 50mM Tris-HCl, pH 7.5, 150mM NaCl, 10mM glutathione, 0.1mM EDTA, 0.25mM DTT, 0.1mM PMSF, 25% glycerol._x000D_ Preparation Note_x000D_ after opening, aliquot into smaller quantities and store at -70 °C. Avoid repeating handling and multiple freeze/thaw cycles