Information AboutSmad4 |
| CATEGORIES ABOUT MOTHERS AGAINST DECAPENTAPLEGIC HOMOLOG 4 | |
| proteins | |
| developmental biology | |
| mh1 domain | |
| mh2 domain | |
SMAD4 or Mothers against decapentaplegic homolog 4 is a 552 ". It belongs to the Darfwin Family of proteins which modulate members of the TGFβ superfamily of proteins, such as Activin or Nodal . It is the only known Mammal ian CoSMAD . Like many other TGFβ family modulators SMAD4 is involved in Cell Signaling . It binds Receptor Regulated SMADs such as SMAD1 or SMAD2 and forms a complex that serves as a Transcription Factor . It promotes binding of the SMAD2 /SMAD4/ FAST-1 complex to DNA . NOMENCLATURE The SMAD proteins are homologs of both the drosophila protein, mothers against decapentaplegic (MAD) and the '' C. Elegans '' protein SMA. The name is a combination of the two. During ''Drosophila'' research, it was found that a mutation in the gene, ''MAD'', in the mother, repressed the gene, '' Decapentaplegic '', in the embryo. The phrase "Mothers against" was added since mothers often form organizations opposing various issues eg. Mothers Against Drunk Driving or (MADD). STRUCTURE FUNCTION SMAD4 binds to Receptor Regulated SMADs (R-SMADs), such as SMAD1 or SMAD2 and facilitates the translocation of the Heteromeric complex into the Nucleus . SMAD4 may form heterotrimeric, heterohexameric or heterodimeric complexes with R-SMADs. Many TGFβ ligands use this Pathway and subsequently SMAD4 is involved in many cell functions such as Differentiation , Apoptosis , Gastrulation , Embryonic Development and the Cell Cycle . DISEASE SMAD4, is often found mutated in many cancers. SMAD4 alterations have been found in multiploid colorectal cancer and Pancreatic Carcinoma . It is also found mutated in the Autosomal Dominant disease Juvenile Polyposis Syndrome (JPS). JPS is characterized by characterized by hamartomatous polyps in the gastrointestinal (GI) tract. These polyps are usually benign, however they are at greater risk of developing Gastrointestinal cancers, in particular colon cancer. REFERENCES Somatic mutations found in human cancers of the MH1 domain of Smad4 have been shown to inhibit the DNA-binding function of this domain. |
|
|