Smad4 and FAST-1 in the assembly of activin-responsive factor

Chen, Xin; Weisberg, Ellen; Fridmacher, Valérie; Watanabe, Minoru; Naco, Grace; Whitman, Malcolm

doi:10.1038/38008

Cited by 538 publications

(440 citation statements)

References 5 publications

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“…This results in their release from the receptor, heterodimerization with the signal mediator Smad4 and subsequent translocation into the nucleus (Liu et al, 1997). Here receptor-activated Smads and Smad4 form complexes with potential co-regulators of transcription such as CBP/p300 (Feng et al, 1998), FAST-1 (Chen et al, 1997) and SKI/SNO (Liu et al, 2001b). The composition of these transcriptional complexes is believed to be largely responsible for the celltype-specific effects of TGFb.…”

Section: Transforming Growth Factor B Signaling Axismentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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Section: Transforming Growth Factor B Signaling Axismentioning

confidence: 99%

Dysregulation of growth factor signaling in human hepatocellular carcinoma

2006

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“…Transforming growth factor-b as well as activin is known to activate activin responsive element (Chen et al, 1997;Itoh et al, 2003). As ELAC2 binds to Smad2, we tested the effect of ELAC2 on Smad2-driven (ARE) 2 -luc reporter activity.…”

Section: Elac2mentioning

confidence: 99%

“…ELAC2 interacts with FAST-1 FAST-1 forms a complex with Smad2 in a TGF-b/ activin-dependent manner to bind to ARE (Chen et al, 1997). To elucidate the mechanism by which ELAC2 could increase (ARE) 2 -luc activity upon ALK5 activation in the presence of FAST-1 and Smad2, we examined whether ELAC2 can also associate with FAST-1 upon ALK5 activation.…”

Section: Elac2mentioning

confidence: 99%

ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-β/Smad-induced growth arrest of prostate cells

et al. 2006

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Transforming growth factor-b (TGF-b) elicits a potent growth inhibitory effect on many normal cells by binding to specific serine/threonine kinase receptors and activating specific Smad proteins, which regulate the expression of cell cycle genes, including the p21 cyclin-dependent kinase (CDK) inhibitor gene. Interestingly, cancer cells are often insensitive to the anti-mitogenic effects of TGF-b for which the molecular mechanisms are not well understood. In this study, we found that the candidate prostate cancer susceptibility gene ELAC2 potentiates TGF-b/Smadinduced transcriptional responses. ELAC2 associates with activated Smad2; the C-terminal MH2 domain of Smad2 interacts with the N-terminal region of ELAC2. Small interfering siRNA-mediated knock-down of ELAC2 in prostate cells suppressed TGF-b-induced growth arrest. Moreover, ELAC2 was shown to specifically associate with the nuclear Smad2 partner, FAST-1 and to potentiate the interaction of activated Smad2 with transcription factor Sp1. Furthermore, activation of the p21 CDK inhibitor promoter by TGF-b is potentiated by ELAC2. Taken together our data indicate an important transcriptional scaffold function for ELAC2 in TGF-b/ Smad signaling mediated growth arrest.

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“…Activin regulation in vivo is known to be mediated by an activin-induced complex, named ARF, that contains both FAST-1/FoxH1, Smad2 and Smad4 (Chen et al, 1996(Chen et al, , 1997Labbe et al, 1998;Weisberg et al, 1998;Liu et al, 1999;Yeo et al, 1999). We tested whether the ARE from intron I of the Xlim-1 gene was able to bind to this complex.…”

Section: Xlim-1 Arementioning

confidence: 99%