DOI: 10.1101/gad.12.19.3084. Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene

Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene

10.1101/gad.12.19.3084

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

Members of the TGF-β superfamily influence a broad range of biological activities including stimulation of wound healing and inhibition of cell growth. TGF-β signals through type I and II receptor serine/ threonine kinases and induces transcription of many genes including plasminogen activator inhibitor-1 (PAI-1). To identify proteins that participate in TGF-β-induced gene expression, we developed a novel retrovirus-mediated expression cloning strategy; and using this approach, we established that transcription factor μE3 (TFE3) is involved in TGF-β-induced activation of the PAI-1 promoter. We showed that TFE3 binds to an E-box sequence in PE2, a 56-bp promoter fragment of the PAI-1 promoter, and that mutation of this sequence abolishes both TFE3 binding as well as TGF-β-dependent activation. TFE3 and Smad3 synergistically activate the PE2 promoter and phosphorylated Smad3 and Smad4 bind to a sequence adjacent to the TFE3-binding site in this promoter. Binding of both TFE3 and the Smad proteins to their cognate sequences is indispensable for TGF-β-inducible activation of the PE2 promoter. Hence, TFE3 is an important transcription factor in at least one TGF-β-activated signal transduction pathway.

Bibliography

Hua, X., Liu, X., Ansari, D. O., & Lodish, H. F. (1998). Synergistic cooperation of TFE3 and Smad proteins in TGF-Î²-induced transcription of the plasminogen activator inhibitor-1 gene. Genes & Development, 12(19), 3084â3095.

Authors 4

Xianxin Hua (first)
Xuedong Liu (additional)
Dominic O. Ansari (additional)
Harvey F. Lodish (additional)

References 44 Referenced 229

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Dates

Type	When
Created	17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 10:24 p.m.)
Indexed	5 days, 14 hours ago (Aug. 28, 2025, 8:27 a.m.)
Issued	26 years, 11 months ago (Oct. 1, 1998)
Published	26 years, 11 months ago (Oct. 1, 1998)
Published Online	26 years, 11 months ago (Oct. 1, 1998)
Published Print	26 years, 11 months ago (Oct. 1, 1998)

Funders 0

None

BibTeX

@article{Hua_1998, title={Synergistic cooperation of TFE3 and Smad proteins in TGF-β-induced transcription of the plasminogen activator inhibitor-1 gene}, volume={12}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.12.19.3084}, DOI={10.1101/gad.12.19.3084}, number={19}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Hua, Xianxin and Liu, Xuedong and Ansari, Dominic O. and Lodish, Harvey F.}, year={1998}, month=oct, pages={3084–3095} }

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  ],
  "subject": [],
  "container-title-short": "Genes Dev.",
  "published": {
    "date-parts": [
      [
        1998,
        10,
        1
      ]
    ]
  }
}