CYTOKINE INDUCIBLE GENES IN HEMATOPOIESIS

描述：（改编自研究者摘要）编码 CIGTA 1（具有转录激活和转录抑制作用的细胞因子诱导基因） 转化活性）在P.I.的实验室， 使用来自鼠T细胞系D10的mRNA的差异显示， 用IL-2受体（IL-2 R）γ链内的细胞因子刺激 超家族 IL-2 R γ链诱导CIGTA 1的表达 细胞因子似乎至少部分通过JAK/Stat介导， 信号通路 CIGTA 1是一种具有转录活性的核蛋白， 激活功能，并可能代表一个新的家庭的创始成员， 转录因子 有趣的是，CIGTA 1的过表达导致了 因子依赖性细胞向非依赖性生长的转化， 失去接触抑制和锚定非依赖性生长 成纤维细胞在软琼脂，证明致癌潜力，这 分子。 PI的长期研究兴趣之一是 了解细胞因子信号传导如何与生物学过程相关， 功能和机制的细胞因子失调在人类疾病。 具有反式激活作用的初级应答基因的克隆， 转换功能允许PI的小组测试以下内容 假设：（1）CIGTA 1可以激活许多下游靶基因， 与不同的蛋白质分子相互作用， 生物过程;（2）不同的功能域可能参与 反式激活、转化、蛋白质-蛋白质相互作用和生物学 由不同生物刺激物介导的功能;和（3） CIGTA 1可被不同的生物刺激物诱导，并且其表达是 由Stat和其他转录因子介导。 为了检验这些假设， 提出（1）鉴定CIGTA 1的细胞靶基因， CIGTA 1相关蛋白;（2）确定CIGTA 1负责的结构域 （3）确定CIGTA 1表达是否可以被 受其他生物刺激物刺激，以及其表达是否与 与细胞分化或细胞周期进展;和（4）确定 Stat结合位点和Stat是否是唯一的顺式DNA元件， 负责CIGTA 1表达的反式作用因子。 阐明 CIGTA 1基因、其基因产物、其细胞靶序列及其 相互作用的蛋白质是必要的充分了解的作用， CIGTA 1在不同的生物过程和各种疾病状态中， 包括癌症

DESCRIPTION: (Adapted from investigator's abstract) The cDNA encoding CIGTA1 (Cytokine lnducible Gene with Transcription Activation and Transformation Activities) was isolated in the P.I.'s laboratory by differential display using mRNAs from a murine T cell line, D10, following stimulation with cytokines within the IL-2 receptor (IL-2R) gamma chain superfamily. The induced expression of CIGTA1 by IL-2R gamma chain cytokines appears to be mediated, at least in part, through the JAK/Stat signaling pathway. CIGTA1 is a nuclear protein with transcriptional activation function and may represent a founding member of a new family of transcription factors. Interestingly, overexpression of CIGTA1 resulted in the conversion of factor-dependent cells to cytokine-independent growth, the loss of contact inhibition and the anchorage-independent growth of fibroblasts in soft agar, demonstrating the oncogenic potential of this molecule. One of the PI's long term research interests has been to understand the process of how cytokine signaling correlates with biological functions and the mechanisms of cytokine dysregulation in human diseases. The cloning of a primary response gene with transactivation and transformation functions allows the PI's group to test the following hypotheses: (1) CIGTA1 can activate many downstream target genes, interact with different protein molecules and in turn, be involved in different biological processes; (2) Different functional domains may be involved in transactivation, transformation, protein-protein interactions and biological functions mediated by different biological stimuli; and (3) Expression of CIGTA1 can be induced by different biological stimuli and the expression is mediated by Stat and other transcription factors. To test these hypotheses, it is proposed to (1) identify cellular target genes for CIGTA1 and ClGTA1-associated proteins; (2) determine the domains of CIGTA1 responsible for its multiple functions; (3) determine whether CIGTA1 expression can be stimulated by other biological stimuli and whether its expression correlates with cell differentiation or cell cycle progression; and (4) determine whether Stat binding site and Stat are the only cis DNA element and transacting factor responsible for CIGTA1 expression. The elucidation of the CIGTA1 gene, its gene product, its cellular target sequences and its interacting proteins is essential for a full understanding of the role of CIGTA1 in different biological processes and various disease states, including cancer.