NOVEL POU PROTEIN AND LYMPHOCYTE GENE EXPRESSION

揭示了调节淋巴细胞的潜在分子机制， 表型和淋巴成熟对于我们理解 免疫功能 已经发现POU结构域蛋白对于 发育和维持特定谱系的成熟表型。 POU蛋白通过调节谱系特异性基因影响发育 通过八聚体或八聚体相关基序表达。 POU突变 基因影响这种相互作用，并导致发育中的畸变。 特定的血统。 八聚体和八聚体样基序在 淋巴细胞特异性基因表达已被充分证明。 已知的淋巴 POU蛋白不能令人满意地解释大多数八聚体依赖性 淋巴特异性基因表达。 我们已经鉴定了一种新的淋巴POU蛋白TCF β 1， 与其他已知的POU蛋白质有远亲关系。 我们在这里提出实验 旨在揭示其在成熟淋巴细胞和T细胞增殖过程中的功能， 发展 这将涉及确定废除《公约》的影响， TCF β 1活性对淋巴表型的影响。 具体而言， 描述了其在调节钙敏感性中的作用， IL 2基因表达的信号通路。 我们还将参与消除TCF β 1在胸腺中的活性， 为了了解TCF β 1在T细胞中的调节作用， 发展 他们将阐明三种不同的 淋巴POU结构域蛋白在T细胞发育中的作用。 这些研究将有助于产生组织培养和免疫小鼠模型， 这有助于阐明淋巴细胞的发育和功能。

Unraveling the underlying molecular mechanisms which regulate the lymphoid phenotype and lymphoid maturation is crucial for our understanding of immune function. POU domain proteins have been found to be critical for development and maintenance of the mature phenotype of specific lineages. POU proteins affect development be regulating lineage specific gene expression via athe octamer or octamer related motifs. Mutation of POU genes affects this interaction and leads to aberrations in development of specific lineages. The importance of octamer and octamer like motifs in lymphocyte specific gene expression is well documented. The known lymphoid POU proteins can not satisfactorily explain most of the octamer dependent lymphoid specific gene expression. We have identified a novel lymphoid POU protein, TCFbeta1 which is distantly related to other known POU proteins. We propose here experiments designed to reveal its function in mature lymphoid cells and during T cell development. This will involve determining the effect of abrogation of TCFbeta1 activity on the lymphoid phenotype. In particular studies are described which address its role in regulating the Calcium sensitive signaling pathway in Il2 gene expression. We will also be involved with abrogate TCFbeta1 activity in thymus of transgenic mice in order to understand athe role of TCFbeta1 in T cell development. They will clarify the comparative roles of three different lymphoid POU domain proteins in T cell development. These studies will help generate tissue culture and mouse models of immune dysfunction which help in elucidating lymphocyte development and function.