Overview:

SMAD4 is a member of the SMAD family and mediates signaling by the transforming growth factor-beta (TGFβ) superfamily and related ligands (1). 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 (2).

Gene Aliases:

JIP, DPC4, MADH4

Genbank Number:

NM_005359

References:

1. Heldin, C.H. et al: TGF-beta signalling from cell membrane to nucleus through SMAD proteins". Nature, 1997, 390 (6659): 465–71.

2. Attisano, L. et al: Mads and Smads in TGF beta signalling". Curr. Opin. Cell Biol. 1998; 10 (2): 188–94.