SMAD4


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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 ?
While SOVA can be congenital or acquired (8, 9), this patient demonstrated no known aortopathy-associated genetic mutations in a specific limited aortopathy panel (ACTA2, CBS, COL3A1, COL5A1, COL5A2, FBN1, FBN2, MYH11, MYLK, PLOD1, SKI, SLC2A10, SMAD3, SMAD4, TGFB2, TGFBR1, TGFBR2; aortopathy panel performed by ARUP Laboratories, Salt Lake City, Utah) (10).
Methods: TGF-[beta]1 and atrogin-1 expression was evaluated by RT-qPCR and/or ELISA; Smad3 phosphorylation by western blot; Smad4 nuclear translocation by indirect immunofluorescence; and ROS levels by DCF probe fluorescent measurements.
The current NeoGenomics offering includes individual gene testing of BRCA1, BRCA2, MLH1, MSH2, EPCAM, MSH6, PMS2 genes as well as a comprehensive 73 gene panel that includes the following genes: AKT1, APC, ATM, ATR, BAP1, BARD1, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, DKN2A, CEBPA, CHEK1, CHEK2, CTNNA1, EPCAM, ETV6, FAM175A, GALNT12, GATA2, GEN1, GREM1, HOXB13, KLLN, MEN1, MLH1, MRE11A, MSH2, MSH6, MUTYH, MYH1, MYH2, MYH3, MYH4, MYH6, MYH7, MYH8, MYH9, MYH10, MYH11, MYH13, MYH14, MYH15, NBN, NTRK1, PALB2, PIK3CA, PMS2, POLD1, POLE, PPM1D, PRSS1, PTEN, RAD50, RAD51, RAD51C, RAD51D, RET, RUNX1, SDHB, SDHC, SDHD, SMAD4, STK11, TERC, TERT, TP53, TP53BP1, VHL, WT1, XRCC2.
Our study also demonstrated that this group has mutations in the TP53 and SMAD4 genes.
They found mutations in the genes TP53 and SMAD4 within oesophageal tumours, offering a way of identifying those patients in which Barrett's
Three main causative genes are known: ENG, ACVRL1 and SMAD4.
Through functional studies and cross-species comparisons of genes found in mice, the researchers found that the progression of prostate cancer can be controlled by inactivation of the genes Smad4 and Pten and activation of the genes cyclinD1 and Spp1.
The liver-specific knockout of smad4 abrogates hepcidin gene transcription resulting in iron overloading (44).
The test identified a total of 214 driver mutations (including multiple mutations in well-known cancer genes such as TP53, STK11, APC, CDH1, ATM, GNAS, SMAD4, PIK3CA, KIT, MDM2 and CDKN2A), of which only 37 (17.
Twenty-four of 47 genes tested had mutations, with the highest rates of mutation observed in TP53 (28%), KRAS (18%), isocitrate dehydrogenase 1 (IDH1, 9%), and SMAD4 (6%).