Gene interactions and pathways from curated databases and text-mining
Mol Cell Biol 2007, PMID: 17438144

Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation.

Zhang, Suping; Fei, Teng; Zhang, Lixia; Zhang, Ran; Chen, Feng; Ning, Yuanheng; Han, Yuna; Feng, Xin-Hua; Meng, Anming; Chen, Ye-Guang

Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta (TGF-beta) signaling by inhibiting TGF-beta signaling at the receptor level. It can interfere with binding to type I receptors and thus activation of receptor-regulated Smads or recruit the E3 ubiquitin ligase Smurf to receptors and thus target them for degradation. Here, we report that Smad7 is predominantly localized in the nucleus of Hep3B cells. The targeted expression of Smad7 in the nucleus conferred superior inhibitory activity on TGF-beta signaling, as determined by reporter assay in mammalian cells and by its effect on zebrafish embryogenesis. Furthermore, Smad7 repressed Smad3/4-, Smad2/4-, and Smad1/4-enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors. An oligonucleotide precipitation assay revealed that Smad7 can specifically bind to the Smad-responsive element via its MH2 domain, and DNA-binding activity was further confirmed in vivo with the promoter of PAI-1, a TGF-beta target gene, by chromatin immunoprecipitation. Finally, we provide evidence that Smad7 disrupts the formation of the TGF-beta-induced functional Smad-DNA complex. Our findings suggest that Smad7 inhibits TGF-beta signaling in the nucleus by a novel mechanism.

Diseases/Pathways annotated by Medline MESH: Carcinoma, Hepatocellular, Liver Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

transforming growth factor beta — Smad7: " Smad7 plays an essential role in the negative-feedback regulation of transforming growth factor beta ( TGF-beta ) signaling by inhibiting TGF-beta signaling at the receptor level "

Smad2/4- ⊣ Smad7: " Furthermore, Smad7 repressed Smad3/4-, Smad2/4- , and Smad1/4 enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors "

Smad3/4- ⊣ Smad7: " Furthermore, Smad7 repressed Smad3/4- , Smad2/4-, and Smad1/4 enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors "

Smad3/4- ⊣ Smad7: " Furthermore, Smad7 repressed Smad3/4- , Smad2/4-, and Smad1/4 enhanced reporter gene expression, indicating that Smad7 can function independently of type I receptors "

Manually curated Databases

  • IRef Biogrid Interaction: SMAD7 — SMAD2 (direct interaction, pull down)
  • IRef Biogrid Interaction: SMAD7 — SMAD4 (direct interaction, pull down)
  • Gene Ontology Complexes transcription factor complex: transcription factor complex complex (ATF7IP-GSC-GCM1-MAFB-NKX2-1-NKX2-5-RARG-KLF4-FOXF1-FOXF2-FOXE3-LDB1-ZFHX3-GATA6-SNAI3-FOXH1-KAT5-AHR-EYA3-NFATC2-CRX-MED27-HES6-SKI-XRCC6-ARNTL-SUB1-JUN-SOX17-SCX-DMBX1-TCF4-TCF7-PDLIM1-TFEB-LBX1-TRRAP-NAA16-EPAS1-MGA-PTF1A-HOXD12-MEF2B-TFDP3-TFDP1-HDAC2-YY1-SMAD9-CLOCK-ONECUT3-SMAD5-SMAD6-SMAD7-SMAD1-SMAD2-PRKDC-RCOR2-NHLH2-REL-TBX5-ARNTL2-BSX-HOXA10-HOXB13-MED23-PUS1-TAL1-RBL1-RBL2-MINA-HMGA1-BARX2-LEF1-EP300-PMF1-ARID5A-WWTR1-LMO2-LMO4-TP73-ABT1-CDK2-DKFZp686M216-CREG1-CTNNB1-SOX9-HAND2-SOX2-TEAD2-MYOG-TEAD4-CEBPA-GFI1B-MYOD1-ALX1-NPAS4-TFAP2D-FIGLA-ALX4-ETS1-PROP1-ASCL3-HCLS1-MSX1-MSX2-SRA1-AJUBA-MTA2-SIN3A-POU3F2-POU3F1-BEX1-MLXIPL-NR2E3-PBX2-ANKRD1-E2F6-E2F5-E2F4-E2F3-E2F2-E2F1-E2F8-CREBBP-ATF5-ATF4-POU2F3)
In total, 8002 gene pairs are associated to this article in curated databases