J Biol Chem 2003,
PMID: 14525983
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.
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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