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.
Current opinion in cell biology, 10(2), 188-194 (1998-04-30)
The discovery of the Mothers against dpp (Mad) gene in Drosophila has opened a window on an entirely unique signalling pathway that functions to mediate responses to the tumour growth factor beta (TGF beta) superfamily. This pathway, which is comprised
The recent identification of the SMAD family of signal transducer proteins has unravelled the mechanisms by which transforming growth factor-beta (TGF-beta) signals from the cell membrane to the nucleus. Pathway-restricted SMADs are phosphorylated by specific cell-surface receptors that have serine/threonine
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