REGULATION OF DIFFERENTIATION OF TRACHEOBRONCHIAL EPITHELIAL CELLS

细胞生物学部分的研究重点是了解细胞的生物学特性。 调节气管支气管分化的分子机制 以及表皮上皮细胞，特别是类维生素A 玩在这个过程中。 维甲酸影响多阶段中的特定阶段 鳞状分化的过程。 这些代理不会阻止 承诺不可逆转地遏制增长，但具体抑制 诱导鳞状细胞特异性基因。 的形成 交联的包膜，一层交联的蛋白质沉积在包膜下， 质膜是鳞状分化的特征。 I型转氨酶基因的启动子，该酶催化 蛋白质交联，已被克隆和测序。 不同区域 将该基因的启动子克隆到报告基因构建体中， 转染到细胞中，以分析哪些元素在 这个基因的转录控制 假定的AP 1和AP 2位点为 发现在该基因的转录控制中是重要的。 的 cDNA克隆SQ 37被表征并发现编码一种新的鳞状细胞- 一种叫做cornifin的蛋白质。 免疫组化和原位 杂交定位cornifin蛋白和mRNA在基底上 几层鳞状分化组织。 Cornifin是一种 一种含有13个重复的八肽（共有）的胞质蛋白 序列，EPCQPKVP）在羧基末端，并且在 脯氨酸和谷氨酰胺。 玉米粉是一种极好的基质， 转氨酶I型，似乎作为前体蛋白的功能， 交联信封 Cornifin似乎是一个基因家族， 克隆了与cornifin具有高度同源性的基因。 制止 维甲酸引起的I型转氨酶在转录水平 水平，似乎是通过核视黄酸受体介导的。 视黄酸对角蛋白表达的抑制似乎发生在 至少部分在转录后水平。 维甲酸选择性用于 特定的类维生素A受体被用来确定哪种受体是 介导类维生素A的各种作用。

The focus of the research in the Cell Biology Section is to understand the molecular mechanisms that regulate the differentiation of tracheobronchial and epidermal epithelial cells and in particular the role that retinoids play in this process. Retinoids affect a specific stage in the multi-stage process of squamous differentiation. These agents do not block the commitment to irreversible growth arrest but specifically suppress the induction of squamous cell-specific genes. The formation of the crosslinked envelope, a layer of crosslinked protein deposited beneath the plasma membrane, is a characteristic feature of squamous differentiation. The promoter of the transglutaminase type I gene, the enzyme that catalyzes the protein crosslinking, has been cloned and sequenced. Different regions of the promoter of this gene were cloned into reporter gene constructs and transfected into cells in order to analyze what elements are important in the transcriptional control of this gene. Putative AP1 and AP2 sites were found to be important in the transcriptional control of this gene. The cDNA clone SQ37 was characterized and found to encode a new squamous cell- specific protein named cornifin. Immunohistochemistry and in situ hybridization localized the cornifin protein and mRNA in the suprabasal layers of several squamous differentiating tissues. Cornifin is a cytosolic protein that contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at the carboxy terminus and is high in the content of proline and glutamine. Cornfin is an excellent substrate for transglutaminase type I and appears to function as a precursor protein for the crosslinked envelope. Cornifin appears to be a gene family since other genes were cloned exhibiting high homology to cornifin. The suppression of transglutaminase type I by retinoic acid occurs at the transcriptional level and appears to be mediated through nuclear retinoic acid receptors. The suppression of cornifin expression by retinoic acid appears to occur at least in part at a post-transcriptional level. Retinoids selective for specific retinoid receptors are being used to determine which receptor is mediating the various effects of retinoids.