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Series GSE685 Query DataSets for GSE685
Status Public on Oct 15, 2003
Title DACH1 inhibits TGF-beta signaling through binding Smad4
Platform organism Homo sapiens
Sample organisms Homo sapiens; Mus musculus
Experiment type Expression profiling by array
Summary 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 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 dot-like 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.
Keywords: other
Contributor(s) Wu K, Yang Y, Wang C, Davoli MA, D'Amico M, Li A, Cveklova K, Kozmik Z, Lisanti MP, Russell RG, Cvekl A, Pestell RG
Citation(s) 14525983
Submission date Sep 26, 2003
Last update date Aug 10, 2018
Contact name Kongming Wu
Phone 202-687-3008
Fax 202-687-4638
Organization name Georgetown University
Department Lombardi Cancer Center & Department of Oncology
Lab Richard Pestell's Lab
Street address 3970 Reservoir Rd, NW
City Georgetown
State/province DC
ZIP/Postal code 20057
Country USA
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (9)
GSM11079 Gene expression regulated by DACH1-2
GSM11364 Gene expression regulated by DACH1-3
GSM11368 Gene expression regulated by DACH1-4
BioProject PRJNA87633

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