PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B
PARP-2 interacts with TTF-1 and regulates expression of surfactant protein-B
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DOI：
10.1074/jbc.m510435200
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发表时间：
2006-04-07
影响因子：
4.8
通讯作者：
Whitsett, JA
中科院分区：
文献类型：
--
作者：
Maeda, Y;Hunter, TC;Whitsett, JA
甲状腺转录因子1（TTF-1/Nkx-2.1）在肺形态发生中起着关键作用，并调节肺特异性基因的表达，包括出生后肺功能所需的表面活性蛋白。TTF-1的活性受其与其他转录因子和共激活因子（包括CBP/p300和SRC-1）相互作用的影响。在这项研究中，我们已经确定了聚（ADP-核糖）聚合酶（PARP-2和PARP-1）作为TTF-1相互作用的蛋白质，影响其转录活性。从转化的小鼠肺上皮细胞（MLE 15）提取物中与TTF-1共免疫沉淀内源性PARP-2，并通过质谱法进行鉴定。PARP-1和Ku 70/Ku 80也与TTF-1从细胞提取物中共免疫沉淀。PARP-2的E结构域通过TTF-1的C-末端结构域相互作用。PARP-1和PARP-2在体外均能增强表面活性蛋白-B（Sftpb基因）启动子的活性，但对其他表面活性蛋白的活性无影响。PARP-2选择性地表达于胚胎第12.5天胎鼠肺的传导和外周肺小管上皮细胞中，并在与表面活性蛋白B一致的细胞部位的成人肺支气管上皮细胞中检测到。PARP-2和PARP-1与TTF-1相互作用并调节肺功能所需的表面活性蛋白B的表达。
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.