FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor β Signals

Liu, Bo; Dou, Changlin; Prabhu, L.; Lai, Eseng

doi:10.1128/mcb.19.1.424

Cited by 84 publications

(54 citation statements)

References 27 publications

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“…These results suggesting that Smad4 does not contribute to the inducible assembly of Smad3 complexes to SBE1 are consistent with reporter assays that also failed to reveal Smad4-dependent activation via SBE1. With regards to Smad2, the failure of the wild-type probe to recruit it could have resulted from the absence of FoxH1 in ␣T3-1 cells, given that FoxH1 is an obligatory cofactor of Smad2 at some downstream targets of TGF-␤ ligands (55)(56)(57). This was not the case, however, because concurrent expression of FoxH1 and encoding Myc-tagged hSmad2 or -3.…”

Section: Discussionmentioning

confidence: 62%

A Smad-binding Element in Intron 1 Participates in Activin-dependent Regulation of the Follistatin Gene

Blount

Vaughan

Vale

et al. 2008

Journal of Biological Chemistry

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Activins are members of the evolutionarily conserved transforming growth factor-␤ (TGF-␤) 3 superfamily of factors implicated in the control of a wide array of cellular processes of embryonic and adult tissues (1-3). Activin A and activin B are homodimers of inhibin ␤A and ␤B subunits, respectively, with established roles in the control of many cell types including those throughout the reproductive axis (1, 4 -6). The inhibin ␤A and ␤B subunits are both expressed in the pituitary and activin B arising from gonadotropes is a critical component of the network of autocrine or paracrine factors of this tissue (7). By exerting control on FSH␤ expression, activin B is hypothesized to locally provide a positive signal for the differential production of FSH over LH and to thereby facilitate the cyclic fluctuations of these hormones during the estrus cycle (7,8). The actions of activins are strictly controlled by the concerted actions and the preferential usage of several extracellular modulators (9, 10). Of these, inhibin and follistatin have established roles in the regulation of pituitary gonadotropes (7).Follistatins are cysteine-rich glycoproteins that bind and bioneutralize activin with high affinity at a 2:1 molar ratio (11-13). They also bind and inactivate myostatin and some bone morphogenetic proteins with varying degrees of affinity (14). Structural studies of the follistatin-activin complex have elucidated the basis for this interaction and provided clues about the determinants of follistatin binding to other ligands (15,16). The follistatin gene comprising 6 exons produces two alternatively spliced mRNA transcripts and the corresponding proteins of 315 or 288 amino acids (FS315 or FS288) (17, 18). The two isoforms, FS315 and FS288, are differentially expressed in most tissues (19,20). The FS315 form is the predominant circulating form, whereas the shorter FS288 form lacking the C-terminal tail associates tightly with heparan sulfate chains of cell surface proteoglycans and is presumed to be the form that acts locally to modulate activin signaling (2,(21)(22)(23). This local function of follistatin is, in turn, controlled by the actions of activin. In cultured rat anterior pituitary cells, activin increases steadystate follistatin mRNA and secreted protein levels (24 -28). Given that inhibin antagonizes the activin-induced rise in pituitary follistatin, this pinpoints gonadotropes as the primary targets of this action of activin (28,29).Activin signals by sequentially binding to activin-specific Type II (ActRII or ActRIIB) then Type I (ALK4) serine/threonine kinase receptors to form a multimeric complex (3,30,31). In this complex, the Type II receptors trans-phosphorylate ALK4 and allow it to transiently interact and phosphorylate the downstream signaling proteins, Smad2 and Smad3, at their C-terminal SSXS motifs (31-33). The phosphorylated forms of Smad2 and Smad3 in turn translocate to the nucleus where they bind to DNA targets and regulate transcription in association with the common Smad4/DPC4 and other p...

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Section: Discussionmentioning

confidence: 62%

A Smad-binding Element in Intron 1 Participates in Activin-dependent Regulation of the Follistatin Gene

Blount

Vaughan

Vale

et al. 2008

Journal of Biological Chemistry

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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%

Regulation of the Lim‐1 gene is mediated through conserved FAST‐1/FoxH1 sites in the first intron

Watanabe

Rebbert

Andreazzoli

et al. 2002

Developmental Dynamics

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“…Smad2 and Smad3 interact directly with cis-acting regulatory elements of certain target genes via the conserved MH1 domain, thus functioning as DNA-binding factors (Feng et al, 1998;Dennler et al, 1998;Labbe et al, 1998;Chen et al, 1999). However, regulation of other TGF-b-responsive genes involves the speci®c interaction of Smads with DNA-binding proteins and coactivators such as FAST-1 (Liu et al, 1997a;Chen et al, 1997;Zhou et al, 1998) and FAST-2 (Labbe et al, 1998;Liu et al, 1999). We recently demonstrated that Smad3 stimulated the activity of the COL1A2 promoter in transiently transfected ®broblasts in the presence or absence of TGF-b (Chen et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Smad-dependent stimulation of type I collagen gene expression in human skin fibroblasts by TGF-β involves functional cooperation with p300/CBP transcriptional coactivators

et al. 2000

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Transforming growth factor-b (TGF-b) stimulation of Type I collagen gene (COL1A2) transcription involves the Smad signal transduction pathway, but the mechanisms of Smad-mediated transcriptional activation are not fully understood. We now demonstrate that the ubiquitous transcriptional coactivators p300 and CREB-binding protein (CBP) enhanced basal as well as TGF-b-or Smad3-induced COL1A2 promoter activity, and stimulated the expression of endogenous Type I collagen. The adenoviral E1A oncoprotein abrogated stimulation of COL1A2 activity in transfected ®broblasts, and reduced the basal level of collagen gene expression. This e ect was due to speci®c interaction of E1A with cellular p300/CBP because (a) a mutant form of E1A defective in p300 binding failed to abrogate stimulation, and (b) forced expression of p300/CBP restored the ability of TGF-b to stimulate COL1A2 promoter activity in the presence of E1A. The e ect of p300 on COL1A2 transcription appeared to be due, in part, to its intrinsic acetyltransferase activity, as stimulation induced by a histone acetyltransferasede®cient mutant p300 was substantially reduced. Transactivation of COL1A2 by p300 involved the Smad signaling pathway, as Smad4-de®cient cells failed to respond to p300, and stimulation was rescued by overexpression of Smad4. Furthermore, minimal constructs containing only the Smad-binding CAGACA element of COL1A2 were transactivated by p300 in the presence of TGF-b. These results indicate, for the ®rst time, that the multifunctional p300/CBP coactivators play a major role in Smad-dependent TGF-b stimulation of collagen gene expression in ®broblasts.

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FAST-2 Is a Mammalian Winged-Helix Protein Which Mediates Transforming Growth Factor β Signals

Cited by 84 publications

References 27 publications

A Smad-binding Element in Intron 1 Participates in Activin-dependent Regulation of the Follistatin Gene

A Smad-binding Element in Intron 1 Participates in Activin-dependent Regulation of the Follistatin Gene

Regulation of the Lim‐1 gene is mediated through conserved FAST‐1/FoxH1 sites in the first intron

Smad-dependent stimulation of type I collagen gene expression in human skin fibroblasts by TGF-β involves functional cooperation with p300/CBP transcriptional coactivators

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