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| 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
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| 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
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| 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 |
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| Submission date |
Sep 26, 2003 |
| Last update date |
Aug 10, 2018 |
| Contact name |
Kongming Wu |
| E-mail(s) |
[email protected]
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| Phone |
202-687-3008
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| Fax |
202-687-4638
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| Organization name |
Georgetown University
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| Department |
Lombardi Cancer Center & Department of Oncology
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| Lab |
Richard Pestell's Lab
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| Street address |
3970 Reservoir Rd, NW
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| City |
Georgetown |
| State/province |
DC |
| ZIP/Postal code |
20057 |
| Country |
USA |
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| Platforms (1) |
| GPL96 |
[HG-U133A] Affymetrix Human Genome U133A Array |
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| Samples (9)
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| GSM11079 |
Gene expression regulated by DACH1-2 |
| GSM11364 |
Gene expression regulated by DACH1-3 |
| GSM11368 |
Gene expression regulated by DACH1-4 |
| GSM11370 |
Gene expression regulated by DACH1-5 |
| GSM11371 |
gene expression regulated by DACH1-6 |
| GSM11373 |
Gene expression regulated by DACH1-7 |
| GSM11374 |
Gene expression regulated by DACH1-8 |
| GSM11375 |
Gene expression regulated by DACH1-9 |
| GSM11376 |
Gene expression regulated by DACH1-1 |
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| Relations |
| BioProject |
PRJNA87633 |
| Supplementary data files not provided |
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