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TGFB1 activates SMAD4. 53 / 64
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"Nuclear and cytoplasm Pitx2 and Smad4 staining was sharply increased with overexpression of Smad4, and treated with TGF-beta1 further increased the Pitx2 and Smad4 levels and induced Pitx2 and Smad4 nuclear import."
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"TGFbeta1 may activate SP1, AP1 and Smad3-Smad4 and thus increase the expression of PAI-1 and collagen I."
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"Interestingly, Smad-4 expression was not altered by deguelin treatment however; deguelin treatment completely blocked TGFbeta1 induced shuttling of Smad4 from cytosol to nucleus (XREF_FIG, right panel)."
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"TGFbeta-1 Treatment Elicits a SMAD4 Dependent EMT in PDAC Cells."
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"While both TGFbeta1 and TGFbeta3 increased binding of Smad4 protein with the p15ink4b promoter, the effect of TGFbeta1 was significantly higher (XREF_FIG) which correlates with its stronger p15ink4b gene activity and protein expression (XREF_FIG and XREF_FIG)."
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"NnV also significantly blocked the upregulation of p-Smad3 and Smad4 induced by TGF-beta1."
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"To define the involvement of ERK1/2 signaling in the Smad4 independent response induced by TGF-beta1, we evaluated the effect of PD98059 pretreatment on p3TP-Lux reporter activity in SW480 cells."
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"While TGFbeta1 and TGFbeta2 increased binding of Smad4 protein with the TBE1 site of c-Myc promoter, the effect of TGFbeta3 was significantly greater (XREF_FIG), as shown by higher levels of immunoprecipiated DNA, indicating that activated Smad4, in response to TGFbeta, binds to the TBE1 site (XREF_FIG)."
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"We investigated whether inactivation of TGF-beta1 by SB inhibitor 431542 suppresses the motility of SMAD4 positive or -negative PDAC cells in vitro."
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"However, addition of TGF-beta1 enhanced the interaction of Smad4 with RBPMS."
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"Western blotting results (XREF_FIG) showed that the stimulation of 10 ng/mL TGF-beta1 increased Smad4, Vimentin, alpha-SMA, collagen I and Timp1 in the three groups of cells, and Smad4 knockdown impaired the increase in these three proteins."
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"TGF-beta1 induced membrane docking of SMAD4."
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"Fluorescence microscopy was used to observe the transfection efficiency and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to observe gene and protein expression levels of alpha-smooth muscle actin (alpha-SMA), E-cadherin, N-cadherin and Smad4, respectively, in HSCs treated with TGF-beta1 or TGF-beta1 and miRNA-122."
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"TGFbeta-1 treatment significantly increased proliferation of the SMAD4 positive Panc-1 cells, while decreasing it in the SMAD4 deficient BxPC-3 cells."
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"The chromatin immunoprecipitation (ChIP) assay further validated that TGF-beta1 induced complexes of Smad2/3 and Smad4 as well as increased binding to the SP1 binding site of the DR5 promoter, whereas siRNA mediated knockdown of SP1 led to decreased binding."
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"Upon TGF-beta1 stimulation in Smad4 knocked down cells, LSR was not reduced and migration was delayed."
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"Furthermore, TGF-beta1 pretreatment can be used to partly rescue the downregulated expression of SMAD4 and EMT markers induced by INTS8 depletion."
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"FoxO3, a member of the Forkhead box (Fox) family, has been found to be a key partner for Smad3 and Smad4, which were activated by TGFbeta1 [XREF_BIBR]."
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"TGF-beta1 being a strong activator of ECM accumulation stimulates the Col 1A2 gene expression by inducing the binding of a Sp1- and p, Smad2/3, Smad4, and containing complex to Col 1A2 upstream promoter element (-330 bp to -286 bp and -271 bp to -255 bp; TGF-beta1 responsive element; TbRE) which contains a CAGA box."
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"In inhibition assays, only the TGF-beta1 signalling inhibitor SB505124 halted the nuclear translocation of its target protein, Smad4, which was induced by IL-6 or TGF-beta1 exposure."
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"Apamin treatment abrogated the activation of p-Smad2/3 and Smad4 induced by TGF-beta1."
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"TGF-beta1 treatment significantly increased levels of collagen I, fibronectin, alpha-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells."
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"In addition, using a self inactivating retrovirus luciferase reporter construct we showed that TGF-beta1 induces Smad4, which then binds to and activates the IL-10 promoter."
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"Although TGFbeta1 stimulus observably increased the SND1, T-Smad2, P-Smad2, Smad4 and MMP2 in SND1-HK cells (P < 0.05 ~ 0.001), these effects of TGFbeta1 were abrogated by SND1-knockdown in SND1-SH cells (P < 0.01 ~ 0.001; Figure XREF_FIG)."
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"To determine whether this downregulation of IDH1 is dependent on canonical TGF-beta signalling, fibroblasts depleted of Smad2, Smad3 or Smad4 were treated with or without TGF-beta1."
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"We found that the gene expression levels of TGF-beta1, its receptor TGF-betaRIotaIota, and the key downstream transcription factor of TGF-beta1 signaling SMAD4 XREF_BIBR, XREF_BIBR, XREF_BIBR were similar in both uPA -/- + DSS and WT + DSS treated mice."
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"TGF-beta1 activated Smad3 and Smad4 signalling to facilitate their nuclear translocation."
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"We found that TGFbeta1 significantly increased binding of Smad4 with all three SBEs in the p15ink4b promoter, whereas TGFbeta3 significantly increased only binding with SBE B. SBE C bound most strongly with Smad4 protein."
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"XREF_BIBR As shown in XREF_FIG, TGF-beta1 was unable to activate the pSBE4-BV and Luc Smad4 reporter."
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"It has been reported recently that TGFbeta1 activated transcription factors Smad3 and Smad4 specifically interact with HNF4alpha and inhibit HNF4alpha trans-activating activity [XREF_BIBR, XREF_BIBR]."
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"Furthermore, DSF/Cu suppressed the nuclear translocation of Smad4 induced by TGF-beta1."
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"As expected, no FSP1 was expressed after TGF-beta1 stimulation in the Smad 2, Smad 3, or Smad 4 knocked down cells."
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"These data, combined with the observation that mutation of TBE1 and 2 decreased luciferase expression by the greatest amount (XREF_FIG), suggest that TBE1 and 2 are the most important regions in the c-Myc promoter for Smad4 mediated transactivation induced by TGFbeta1 signaling in UMSCC38 cells, but not in UMSCC11B cells."
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"This observation was further confirmed by immunofluorescent analysis showing that DDK and DLX1 was predominantly localized in the nucleus, and co-localized with GFP and SMAD4 when the SKOV3 and OVCA433 cells were treated with TGF-beta1 (5ng/ml, 3h; XREF_FIG)."
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"To probe the arrays, we performed different ChIP assays by using an antibody against SMAD4 in immortalized ovarian surface epithelial (IOSE) cells treated with TGF-beta 1 for 0 and 3 hrs."
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"We found that LJP61A suppressed TGF-β1-induced activation of Smad3, Smad4 and p38MAPK in vitro and in vivo."
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"Since mutation SBE C decreased luciferase expression most (XREF_FIG) it appears that site C is the most important region in the p15ink4b promoter for Smad4 mediated transactivation induced by TGFbeta1 signaling."
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"TGF-beta1 induced nuclear localization of WWOX and Smad4 in HCT116 cells, and the nuclear level of Hyal-2 was low also."
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"TGFbeta1 induces Smad4 transactivation of the p15ink4b promoter."
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"FoxO3, a member of the Forkhead box (Fox) family, has been found to be a key partner for Smad3 and Smad4, which were activated by TGFβ1 [ xref ]."
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"Smad2, Smad3, and Smad4 are present and activated by TGF-beta1 in human mesangial cells."
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"Smad2, Smad3 and Smad4 are present and activated by TGF-beta1 in MDPC-23 cells."
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"We demonstrate that TGF-beta1 promotes a Smad4 dependent up-regulation of DDR1, together with LOXL2, in cultured HCC cells."
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"Knockdown of AUF1 demonstrated no obvious effect on the expression of coactivator Smad4, or inhibitor Smad7 in HK2 cells treated with vehicle or TGF-beta1."
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"For instance, TGF-β1-activated Smad3 and Smad4 were found to bind specifically to the second promoter region of the p53 E3 ligase human murine double minute (HDM2), causing increased HDM2 protein expression and destabilization of p53 in human cancer cell lines."
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"Specifically, normal nuclear accumulation of Smad2 and Smad4 heterocomplexes induced by TGF-beta1 is involved in carcinogenesis."
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"However, TGF-beta1 upregulated the expression of the SMAD4 nucleoprotein compared with the control, and vorinostat inhibited this upregulation of the SMAD4 nucleoprotein caused by TGF-beta1 (XREF_FIG, right)."
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"To test if TGF-beta-induced upregulation of SHIP1 and IRAK-M is dependent on SMAD4, shSMAD4 and shLUC THP1 cells were treated with TGF-beta1 (1ng/ml) for 0, 3, 6 and 24 hours."
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"That is, TGF-beta1 activated the overexpressed Smad4 to cause apoptosis."
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"TGF-beta1 stimulates the p 15Ink4B expression by inducing a complex assembly of Smad2, Smad3, Smad4, and Sp1 on its promoter."
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"It has been reported recently that TGFβ1-activated transcription factors Smad3 and Smad4 specifically interact with HNF4α and inhibit HNF4α trans -activating activity [ xref , xref ]."
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"Smad4 is an important molecule of the TGF-beta and Smad signaling pathway and TGF-beta1 induced the upregulation of Smad4, which is a marker of this signaling pathway."
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"The results of luciferase reporter experiments and ChIP assays demonstrated that TGFbeta1 promoted the binding of Smad4 to the miR-155 promoter at a site located in 454 bp from the transcription start site in vivo, further verifying that miR-155 is a transcriptional target of the TGFbeta1 and Smad4 pathway."
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