Smad4
Smad4 (SMAD family member 4, also known as DPC4 and MADH4) is the common SMAD, or co-SMAD, of the dwarfin/SMAD family. It mediates transcriptional responses to TGF-beta and bone morphogenetic protein signalling and acts as a tumour suppressor. Browse Assay Genie's current range of Smad4 research reagents below, or read on for the biology behind the target.
Smad4 is the coactivator and mediator of signal transduction by transforming growth factor (TGF)-beta. Receptor-regulated SMAD proteins are phosphorylated and activated by transmembrane serine-threonine receptor kinases. The Smad4 protein then forms homomeric complexes, and heteromeric complexes with other activated SMADs, which accumulate in the nucleus and regulate the transcription of target genes. The heterotrimeric SMAD2/SMAD3-SMAD4 complex forms in the nucleus and is required for TGF-mediated signalling. Smad4 promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. It is also a component of the SMAD3/SMAD4/JUN/FOS complex at the AP1 promoter site, which is needed for synergistic transcriptional activity in response to TGF-beta.
The Smad4 protein binds DNA and recognises an 8-bp palindromic sequence, GTCTAGAC, called the Smad-binding element (SBE). It is a crucial component of the bone morphogenetic protein (BMP) pathway, where it acts synergistically with SMAD1 and YY1 in BMP-mediated cardiac-specific gene expression. In muscle, it helps balance atrophy and hypertrophy: recruitment by MSTN promotes atrophy through phosphorylated SMAD2/4, whereas BMP pathway recruitment promotes hypertrophy through phosphorylated SMAD1/5/8. Smad4 also positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ. Smad proteins are subject to complex regulation by post-translational modification.
The Smad4 gene is also known by the symbols DPC4 and MADH4, and by the earlier names MAD and SMAD, mothers against decapentaplegic homolog 4. The protein acts as a tumour suppressor and inhibits epithelial cell proliferation. It may also restrain tumours by reducing angiogenesis and increasing blood vessel hyperpermeability. Mutations or deletions in the gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia syndrome.
Smad4 is the co-SMAD that partners SMAD2/SMAD3 in the nucleus, so it is central to dissecting TGF-beta-driven transcription.
Smad4 is a crucial component of BMP signalling and acts with SMAD1 and YY1 in BMP-mediated cardiac gene expression.
Smad4 acts as a tumour suppressor, and its mutation or deletion is linked to pancreatic cancer and juvenile polyposis syndrome.
Smad4 is recruited by MSTN or the BMP pathway, placing it at the balance point between muscle atrophy and hypertrophy.
Smad4 is the common SMAD that mediates TGF-beta and BMP signalling. It forms complexes with activated receptor-regulated SMADs, accumulates in the nucleus, binds the Smad-binding element and regulates transcription of target genes. It also acts as a tumour suppressor and inhibits epithelial cell proliferation.
Smad4 is also called DPC4 and MADH4. Earlier HGNC names include MAD and SMAD, mothers against decapentaplegic (or DPP) homolog 4 (Drosophila). The current HGNC name is SMAD family member 4, and the protein belongs to the dwarfin/SMAD family.
Mutations or deletions in the Smad4 gene have been shown to result in pancreatic cancer, juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia syndrome. Mouse and rat both have a Smad4 ortholog; check the datasheet of any product for its validated reactivity.
Other SMAD family members, including receptor-regulated and inhibitory SMADs that work with Smad4 in TGF-beta and BMP signalling.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q13485; product specifications from Assay Genie datasheets.