Document Detail

The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells.
MedLine Citation:
PMID:  16630564     Owner:  NLM     Status:  MEDLINE    
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.
Meng-Chun Yang; Yuhong Guo; Chia-Chi Liu; Jonathan C Weissler; Yih-Sheng Yang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-04-04
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  344     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-01     Completed Date:  2006-06-22     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  484-90     Citation Subset:  IM    
Department of Internal Medicine, Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, TX 75390-9034, USA.
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MeSH Terms
Cells, Cultured
Lung / metabolism*
Nuclear Proteins / genetics,  metabolism*
Promoter Regions, Genetic / genetics
Pulmonary Surfactant-Associated Protein B / genetics,  metabolism*
Pulmonary Surfactant-Associated Protein C / genetics,  metabolism*
Transcription Factors / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/CCDC59 protein, human; 0/Nuclear Proteins; 0/Pulmonary Surfactant-Associated Protein B; 0/Pulmonary Surfactant-Associated Protein C; 0/Transcription Factors; 0/thyroid nuclear factor 1

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