Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2003, PMID: 14525983

DACH1 inhibits transforming growth factor-beta signaling through binding Smad4.

Wu, Kongming; Yang, Ying; Wang, Chenguang; Davoli, Maria A; D'Amico, Mark; Li, Anping; Cveklova, Kveta; Kozmik, Zbynek; Lisanti, Michael P; Russell, Robert G; Cvekl, Ales; Pestell, Richard G

The vertebrate homologues of Drosophila dachsund, DACH1 and DACH2, have been implicated as important regulatory genes in development. DACH1 plays a role in retinal and pituitary precursor cell proliferation and DACH2 plays a specific role in myogenesis. DACH proteins contain a domain (DS domain) that is conserved with the proto-oncogenes Ski and Sno. Since the Ski/Sno proto-oncogenes repress AP-1 and SMAD signaling, we hypothesized that DACH1 might play a similar cellular function. Herein, DACH1 was found to be expressed in breast cancer cell lines and to inhibit transforming growth factor-beta (TGF-beta)-induced apoptosis. DACH1 repressed TGF-beta induction of AP-1 and Smad signaling in gene reporter assays and repressed endogenous TGF-beta-responsive genes by microarray analyses. DACH1 bound to endogenous NCoR and Smad4 in cultured cells and DACH1 co-localized with NCoR in nuclear dotlike structures. NCoR enhanced DACH1 repression, and the repression of TGF-beta-induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain. The DS domain of DACH was sufficient for NCoR binding at a Smad4-binding site. Smad4 was required for DACH1 repression of Smad signaling. In Smad4 null HTB-134 cells, DACH1 inhibited the activation of SBE-4 reporter activity induced by Smad2 or Smad3 only in the presence of Smad4. DACH1 participates in the negative regulation of TGF-beta signaling by interacting with NCoR and Smad4.

Document information provided by NCBI PubMed

Text Mining Data

transforming growth factor-beta ⊣ DACH1: " DACH1 inhibits transforming growth factor-beta signaling through binding Smad4 "

AP-1 ⊣ DACH1: " DACH1 repressed TGF-beta induction of AP-1 and Smad signaling in gene reporter assays and repressed endogenous TGF-beta-responsive genes by microarray analyses "

Smad ⊣ DACH1: " DACH1 repressed TGF-beta induction of AP-1 and Smad signaling in gene reporter assays and repressed endogenous TGF-beta-responsive genes by microarray analyses "

NCoR ⊣ DACH1: " NCoR enhanced DACH1 repression, and the repression of TGF-beta induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain "

NCoR ⊣ AP-1: " NCoR enhanced DACH1 repression, and the repression of TGF-beta induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain "

NCoR ⊣ Smad: " NCoR enhanced DACH1 repression, and the repression of TGF-beta induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain "

AP-1 ⊣ DACH1: " NCoR enhanced DACH1 repression, and the repression of TGF-beta induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain "

Smad ⊣ DACH1: " NCoR enhanced DACH1 repression, and the repression of TGF-beta induced AP-1 or Smad signaling by DACH1 required the DACH1 DS domain "

DACH1 ⊣ Smad4: " Smad4 was required for DACH1 repression of Smad signaling "

Smad ⊣ Smad4: " Smad4 was required for DACH1 repression of Smad signaling "

Manually curated Databases

  • OpenBEL Selventa BEL large corpus: O/- complex () → SKI (decreases, SKI Activity)
    Evidence: the Ski/Sno proto-oncogenes repress AP-1 and SMAD signaling
  • OpenBEL Selventa BEL large corpus: O/- complex () → SKIL (decreases, SKIL Activity)
    Evidence: the Ski/Sno proto-oncogenes repress AP-1 and SMAD signaling
  • OpenBEL Selventa BEL large corpus: O/- complex () → NCOR1 (decreases, NCOR1 Activity, Activity)
    Evidence: NCoR enhanced DACH1 repression
  • IRef Biogrid Interaction: SKI — SIN3A (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SKI — NCOR1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SIN3A — DACH1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: DACH1 — NCOR1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SMAD3 — DACH1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SMAD4 — DACH1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SMAD4 — DACH1 (direct interaction, pull down)
  • IRef Biogrid Interaction: SKI — SMAD3 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: SKI — SMAD4 (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: SKI — NCOR1 (in vivo)
  • IRef Hprd Interaction: DACH1 — SIN3A (in vivo)
  • IRef Hprd Interaction: DACH1 — NCOR1 (in vivo)
  • IRef Hprd Interaction: DACH1 — SMAD3 (in vivo)
  • IRef Hprd Interaction: DACH1 — SMAD4 (in vivo)
  • IRef Hprd Interaction: DACH1 — SMAD4 (in vitro)
  • IRef Intact Interaction: SKI — SIN3A (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: SKI — NCOR1 (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: DACH1 — SIN3A (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: NCOR1 — DACH1 (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: SMAD3 — DACH1 (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: DACH1 — SMAD4 (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: DACH1 — SMAD4 (physical association, pull down)
  • IRef Intact Interaction: SMAD3 — SKI (physical association, coimmunoprecipitation)
  • IRef Intact Interaction: SKI — SMAD4 (physical association, coimmunoprecipitation)
In total, 8 gene pairs are associated to this article in curated databases