title: PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B.
abstract: Thyroid transcription factor 1 (TTF-1/Nkx-2.1) plays a critical role in lung morphogenesis and regulates the expression of lung-specific genes, including the surfactant proteins required for pulmonary function after birth. The activity of TTF-1 is influenced by its interactions with other transcription factors and coactivators, including CBP/p300 and SRC-1. In this study, we have identified poly(ADP-ribose) polymerases (PARP-2 and PARP-1) as TTF-1 interacting proteins that influence its transcriptional activity. Endogenous PARP-2 was coimmunoprecipitated from transformed mouse lung epithelial cell (MLE15) extracts with TTF-1 and was identified by mass spectrometry. PARP-1 and Ku70/Ku80 were also coimmunoprecipitated from the cell extracts with TTF-1. The E domain of PARP-2 interacted via the C-terminal domain of TTF-1. Both PARP-1 and PARP-2 enhanced the activity of the promoter of surfactant protein-B (Sftpb gene) but not other surfactant proteins in vitro. PARP-2 was selectively expressed in epithelial cells of the conducting and peripheral lung tubules of the fetal mouse lung from embryonic day 12.5 and was detected in bronchial epithelial cells in the adult lung at cellular sites consistent with that of surfactant protein B. PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a protein required for lung function.
authors.affiliation: Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Maeda
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Hunter
authors.forename: David E
authors.initials: DE
authors.lastname: Loudy
authors.forename: Vrushank
authors.initials: V
authors.lastname: Davé
authors.forename: Valérie
authors.initials: V
authors.lastname: Schreiber
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Whitsett
mesh_terms: D000818:Animals; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D047468:Immunoprecipitation; D008168:Lung / Q000502:physiology; D051379:Mice; D009687:Nuclear Proteins / Q000502:physiology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000502:physiology*; D037701:Pulmonary Surfactant-Associated Protein B / Q000096:biosynthesis*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: C000614412:NKX2-1 protein, human; C000614414:Nkx2-1 protein, mouse; D009687:Nuclear Proteins; D037701:Pulmonary Surfactant-Associated Protein B; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C499320:PARP1 protein, human; C483041:PARP2 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases