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.

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SMAD4 gene inactivation or deletion is associated with a worse prognosis in invasive PDAC.

Classification, Morphology, Molecular Pathogenesis, and Outcome of Premalignant Lesions of the Pancreas

sup][32] Another miRNA (miR-146a) also suppressed TGF-[sz]-induced HSC activation and hepatic fibrosis development by targeting Smad4 .

Regulatory Mechanisms of the Molecular Pathways in Fibrosis Induced by MicroRNAs

Previous research had identified mutations in genes such as SMAD4 as potential risk factors for highly aggressive and invasive PDAC tumors, likely because these mutations weaken TGF-?

United States : Gene Mutation Makes Tumors Tense, Worsens Patient Prognosis

Activated ALK4 phosphorylates intracellular signaling molecules, Smad2/3, which, in turn, form a complex with the coactivator, Smad4.

Two activin type 2B receptors from sea bream function similarly in vitro

Furthermore, SIRT1 deacetylates and suppresses Smad4, a key molecule in TGF-[beta] signaling, which lowers the expression of target genes [47].

Cross Talk Mechanism among EMT, ROS, and Histone Acetylation in Phorbol Ester-Treated Human Breast Cancer MCF-7 Cells

Gauthier, "Direct binding of Smad3 and Smad4 to critical TGF[beta]-inducible elements in the promoter of human plasminogen activator inhibitor-type 1 gene," The EMBO Journal, vol.

Kruppel-like factor 4 inhibits the transforming growth factor-[beta]1-promoted epithelial-to-mesenchymal transition via downregulating plasminogen activator inhibitor-1 in lung epithelial cells

A number of important direct miRNA-mRNA regulations were described in PTC, as hsa-miR-155 downregulating APC (adenomatous polyposis coli), THRB (thyroid hormone receptor beta) regulation by hsa-miR-21 and hsa-miR-146a, or hsa-miR-146b-5p regulating SMAD4 (SMAD family member 4) [17-19].

Differences in miRNA and mRNA profile of papillary thyroid cancer variants

SMAD4 downstream signal protein of the TGF superfamily is an essential factor for mediating the TGF-AY superfamily signaling.

IMMUNOLOCALIZATION OF THE SMAD4 PROTEIN IN POSTNATAL PORCINE UTERUS

They found mutations in the genes TP53 and SMAD4 within oesophageal tumours, offering a way of identifying those patients in which Barrett's

Southampton Varsity discovers mutations that can cause oesophageal cancer

Three main causative genes are known: ENG, ACVRL1 and SMAD4.

Hereditary haemorrhagic telangiectasia in North African and sub-Saharan patients

Confirmation of the diagnosis is obtained through genetic tests for endoglin mutations, ALK-1 or SMAD4 genes.

Septoplastia con injerto de dura sintetica en epistaxis por telangiectasias hemorragicas hereditarias

Las otras posibles causas asociadas a CGDH se deben a mutaciones asociadas a proteinas de adhesion que interactuan con la E-cadherina y genes que no se encuentran relacionados con esta proteina como p53, SMAD4, MET y BRCA2 [16].