The TTF-1/TAP26 complex differentially modulates surfactant protein-B (SP-B) and -C (SP-C) promoters in lung cells.
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.
Yang
Meng-Chun
MC
Department of Internal Medicine, Pulmonary and Critical Care Medicine, UT Southwestern Medical Center, Dallas, TX 75390-9034, USA.
Guo
Yuhong
Y
Liu
Chia-Chi
CC
Weissler
Jonathan C
JC
Yang
Yih-Sheng
YS
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D008168:Lung / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D037701:Pulmonary Surfactant-Associated Protein B / Q000235:genetics / Q000378:metabolism*; D037721:Pulmonary Surfactant-Associated Protein C / Q000235:genetics / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
C511144:CCDC59 protein, human; C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D037721:Pulmonary Surfactant-Associated Protein C; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors