The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells

Meng Chun Yang, Yuhong Guo, Chia Chi Liu, Jonathan C. Weissler, Yih Sheng Yang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Surfactant protein-B (SP-B) and -C (SP-C) are small hydrophobic surfactant proteins that maintain surface tension in alveoli. Both SP-B and SP-C are regulated by a key factor, thyroid transcription factor-1 (TTF-1), in lung cells. Previously, we identified a 26-kDa, TTF-1-associated protein (TAP26) that was shown to interact with TTF-1 and enhance TTF-1-transactivated SP-B promoter activity. In this study, we hypothesized that TAP26 could also serve as a co-activator of the SP-C promoter. Using the chromatin immunoprecipitation assay (ChIP), we demonstrated that TAP26 was not only a component of the SP-B promoter, but was also a component of the SP-C promoter complex in lung cells. TAP26 could synergistically stimulate TTF-1-activated SP-B and SP-C promoter activities in H441 cells (a lung adenocarcinoma cell). However, in MLE12 cells (a murine lung type II cell), only SP-B, but not SP-C, promoter activity was improved by TAP26 in a concentration-dependent manner. This result indicated that the TTF-1/TAP26 complex-activated SP-C promoter activity was already optimized in MLE12 cells and that the response of the SP-C promoter to the complex was different from that of the SP-B promoter. Via promoter mutation analysis, adjacent TTF-1 binding sites within the proximal promoter region of SP-C were found to be essential for TTF-1/TAP26-enhanced SP-C promoter activity. Thus, a dimerized complex structure was needed for advanced promoter activity. This result also provided a molecular mechanism by which both the SP-B and SP-C promoters could be differentially regulated by the same complex.

Original languageEnglish (US)
Pages (from-to)484-490
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume344
Issue number2
DOIs
StatePublished - Jun 2 2006

Keywords

  • Gene regulation
  • Surfactant protein-B
  • Surfactant protein-C
  • TAP26
  • TTF-1

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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