Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription
- PMID: 9732876
- DOI: 10.1038/29814
Smad3 and Smad4 cooperate with c-Jun/c-Fos to mediate TGF-beta-induced transcription
Erratum in
- Nature 1998 Dec 3;396(6710):491
Abstract
Smad proteins transduce signals for transforming growth factor-beta (TGF-beta)-related factors. Smad proteins activated by receptors for TGF-beta form complexes with Smad4. These complexes are translocated into the nucleus and regulate ligand-induced gene transcription. 12-O-tetradecanoyl-13-acetate (TPA)-responsive gene promoter elements (TREs) are involved in the transcriptional responses of several genes to TGF-beta (refs 5-8). AP-1 transcription factors, composed of c-Jun and c-Fos, bind to and direct transcription from TREs, which are therefore known as AP1-binding sites. Here we show that Smad3 interacts directly with the TRE and that Smad3 and Smad4 can activate TGF-beta-inducible transcription from the TRE in the absence of c-Jun and c-Fos. Smad3 and Smad4 also act together with c-Jun and c-Fos to activate transcription in response to TGF-beta, through a TGF-beta-inducible association of c-Jun with Smad3 and an interaction of Smad3 and c-Fos. These interactions complement interactions between c-Jun and c-Fos, and between Smad3 and Smad4. This mechanism of transcriptional activation by TGF-beta, through functional and physical interactions between Smad3-Smad4 and c-Jun-c-Fos, shows that Smad signalling and MAPK/JNK signalling converge at AP1-binding promoter sites.
Similar articles
-
Smad3/AP-1 interactions control transcriptional responses to TGF-beta in a promoter-specific manner.Oncogene. 2001 Jun 7;20(26):3332-40. doi: 10.1038/sj.onc.1204448. Oncogene. 2001. PMID: 11423983
-
Induction of the AP-1 members c-Jun and JunB by TGF-beta/Smad suppresses early Smad-driven gene activation.Oncogene. 2001 Apr 26;20(18):2205-11. doi: 10.1038/sj.onc.1204347. Oncogene. 2001. PMID: 11402315
-
Functional cooperation between Smad proteins and activator protein-1 regulates transforming growth factor-beta-mediated induction of endothelin-1 expression.Circ Res. 2003 Jun 27;92(12):1288-95. doi: 10.1161/01.RES.0000078491.79697.7F. Epub 2003 May 22. Circ Res. 2003. PMID: 12764024
-
Encounters with Fos and Jun on the road to AP-1.Semin Cancer Biol. 1990 Feb;1(1):19-26. Semin Cancer Biol. 1990. PMID: 2133107 Review.
-
fos-jun Conspiracy: implications for the cell.Princess Takamatsu Symp. 1989;20:119-26. Princess Takamatsu Symp. 1989. PMID: 2518685 Review.
Cited by
-
Single-cell multiomics reveals the complexity of TGFβ signalling to chromatin in iPSC-derived kidney organoids.Commun Biol. 2022 Nov 27;5(1):1301. doi: 10.1038/s42003-022-04264-1. Commun Biol. 2022. PMID: 36435939 Free PMC article.
-
Molecular mechanisms of MMP9 overexpression and its role in emphysema pathogenesis of Smad3-deficient mice.Am J Physiol Lung Cell Mol Physiol. 2012 Jul;303(2):L89-96. doi: 10.1152/ajplung.00060.2012. Epub 2012 May 18. Am J Physiol Lung Cell Mol Physiol. 2012. PMID: 22610349 Free PMC article.
-
Regulation of TGFβ Signalling by TRPV4 in Chondrocytes.Cells. 2021 Mar 24;10(4):726. doi: 10.3390/cells10040726. Cells. 2021. PMID: 33805168 Free PMC article.
-
Tethering of the conserved piggyBac transposase fusion protein CSB-PGBD3 to chromosomal AP-1 proteins regulates expression of nearby genes in humans.PLoS Genet. 2012 Sep;8(9):e1002972. doi: 10.1371/journal.pgen.1002972. Epub 2012 Sep 27. PLoS Genet. 2012. PMID: 23028371 Free PMC article.
-
In vivo regulation of gene expression and T helper type 17 differentiation by RORγt inverse agonists.Immunology. 2015 Jul;145(3):347-56. doi: 10.1111/imm.12444. Epub 2015 Apr 3. Immunology. 2015. PMID: 25604624 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous
