SMAD4

(redirected from MADH4)

SMAD4

A gene on chromosome 18q21.1 that encodes a SMAD family protein, named for their similarity to the Drosophila gene Mothers Against Decapentaplegic (MAD), which are signal transducers and transcription modulators of multiple signalling pathways. SMAD4 forms homomeric complexes and heteromeric complexes with other activated SMADs; these accumulate in the nucleus and regulate target gene transcription. SMAD4 binds to DNA and recognizes an 8-bp palindromic sequence, the SMAD-binding element (SBE).
 
Molecular pathology
SMAD4 mutations or deletions are linked to hereditary haemorrhagic telangiectasia syndrome, juvenile polyposis syndrome and pancreatic cancer.
References in periodicals archive ?
Griffin et al., "Evaluation of candidate genes MAP2K4, MADH4, ACVR1B, and BRCA2 in familial pancreatic cancer: deleterious BRCA2 mutations in 17%," Cancer Research, vol.
A combined syndrome of juvenile polyposis and hereditary haemorrhagic telangiectasia associated with mutations in MADH4 (SMAD4).
Ahmed et al., "The prevalence of MADH4 and BMPR1A mutations in juvenile polyposis and absence of BMPR2, BMPR1B, and ACVR1 mutations," Journal of Medical Genetics, vol.
Missense mutations of MADH4: characterization of the mutational hot spot and functional consequences in human tumors.
as follows: Factor V, 5'-GCCCAGTGCTTAACAAGACCA-3' and 5'-AAGGTTACTTCAAGGACAAAATAC-3'; BRCA2, 5'-TATAGGGAAGCTTCATAAGTCAG-3' and 5'-ACCACCTTCAACATTTAAGTTATT-3'; FLT3, 5'-GCAATTTAGGTATGAAAGCCAGC-3' and 5'-CTTTCAGCATTTTGA000CAACC-3'; MADH4, 5'-TGAAATCATAAGATGACATCTATGAATG-3' and 5'-TCCGGGATGGGGCGGCATAG-3'; 16S ribosomal DNA, 5'-CACAAGCGGTGGAGCATGTGG-3' and 5'-AGGCCCGGGAACGTATTCAC-3'.
These included mutations such as FLT3 internal tandem duplication mutations, which occur in ~20% of acute myeloid leukemias, and point mutations in MADH4, which commonly occur in pancreatic cancer.
(44,45) The targets of these losses include the tumor suppressor genes p16/CDKN2A on chromosome 9p, (46) DPC4 (SMAD4, MADH4) on chromosome 18q, (47) TP53 and MKK4 on chromosome 17p, (48,49) and BRCA2 on chromosome 13q.
DPC4 (SMAD4, MADH4) is a tumor suppressor gene that encodes for a critical transcription factor involved in the TGF-[beta] signal pathway.