MHC Class II Transactivator Function & Regulation

描述(由申请人提供)：MHC II类反式激活剂(CIITA)是一种 关键转录因子调节至关重要的基因的表达 为了免疫反应和建立正常的免疫平衡 对宿主的控制。CIITA激活抗原相关基因的表达 但抑制Th2型细胞因子和FasL的表达。我们和 其他人则表明，CIITA作为激活者和 组蛋白乙酰转移酶与CIITA相互作用介导的抑制子 CBP/p300。最近，我们和其他人还观察到，CIITA与 赛尔夫。CITA自结合缺陷突变体未能激活MHC 第二类启动子表明自关联能力与 CIITA的反式激活潜能。因此，理解CIITA活动是如何 受到多重互动的调节与理解有很大关系 免疫反应是如何被CIITA调节的。 在当前的应用中，我们提出了总体目标为实验 认识CIITA的结构和功能规范目标 基因表达。第一，分子间和分子内 控制CIITA的交互，并通过该信息激活CIITA 作为转录调节的功能，将通过基因， 生物化学和分子生物学的方法。第二，机制 细胞以活性和/或非活性形式保留CIITA蛋白，并对 通过磷酸化调节CIITA活性的信号将被研究。 第三，我们将使用荧光技术检测活细胞中的ciita相互作用。 共振能量传递。此应用程序中描述的实验将 洞察CIITA如何感知和响应发生的刺激 在免疫反应和疾病状态期间，维持细胞调节。

DESCRIPTION (provided by applicant): MHC class II transactivator (CIITA) is a critical transcription factor regulating the expression of genes that are vital to immune responses and for the establishment of normal immune homeostatic controls of a host. CIITA activates the expression of genes involved in antigen presentation but represses the expression of Th2 type cytokine and FasL. We and others have demonstrated that the activity of CIITA as an activator and a repressor is mediated by CIITA interaction with histone acetyltransferase CBP/p300. Recently, we and others also observed that CIITA forms a complex with self. CIITA mutants defective in self-association failed to activate the MHC class II promoter suggesting that the ability of self-association is linked to transactivation potential of CIITA. Therefore, understanding how CIITA activity is regulated by multiple interactions has great relevance towards understanding how immune response is modulated by CIITA. In the current application, we propose experiments with the overall objective of understanding the structure and function of CIITA to regulate the target gene expression. First, the mechanisms by which inter- and intra molecular interaction of CIITA is controlled and this information to activate CIITA function as a transcriptional regulator, will be explored through genetic, biochemical and molecular biology approaches. Secondly, the mechanisms whereby cells retain CIITA protein in an active and/or inactive form and respond to a signal to regulate CIITA activity by phosphorylation, will be investigated. Thirdly, we will examine CIITA interaction in living cells using fluorescence resonance energy transfer. The experiments described in this application will provide insight into how CIITA senses and responds to stimulus that occur during immune response, and disease states, to maintain cellular regulation.