Number of the records: 1
DACH1 inhibits transforming growth factor-beta signaling through binding Smad4
- 1.
SYSNO ASEP 0105361 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Ostatní články Title DACH1 inhibits transforming growth factor-beta signaling through binding Smad4 Title DACH1 potlačuje přenos signálu transformujícího růstového faktoru beta vazbou na Smad4 Author(s) Wu, K. (US)
Yang, Y. (US)
Wang, C. (IL)
Davoli, M. A. (US)
D'Amico, M. (US)
Li, A. (US)
Cveklova, K. (US)
Kozmik, Zbyněk (UMG-J) RID
Lisanti, M. P. (US)
Russell, R. G. (US)
Cvekl, A. (US)
Pestell, R. G. (US)Source Title Journal of Biological Chemistry. - : Elsevier - ISSN 0021-9258
Roč. 278, č. 51 (2003), s. 51673-51684Number of pages 12 s. Language eng - English Country US - United States Keywords Dach1, smad Subject RIV EB - Genetics ; Molecular Biology R&D Projects LN00A079 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Annotation The vertebrate homologues of Drosophila dachshund, 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 Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2005
Number of the records: 1