PDGF REGULATION OF THE C FOS PROTOONCOGENE BY SIF/P91

细胞生物学和癌症研究中的一个主要问题是 从细胞表面传递到细胞核的信号来调节 特定的基因表达。在此之前，我的实验室已经确定了一种PDGF 一种被称为SIF的诱导因子，它参与调节c- Fos原癌基因。SIF因子具有快速诱导的DNA结合 在没有新的蛋白质合成的情况下被激活的活性。它是 作为细胞表面和细胞表面之间直接中间体的候选人 原子核。我们自己和其他人已经表明，这个因素可以做出反应 不仅与PDGF有关，还与其他多肽生长因子如EGF有关， 胰岛素、脑脊液-L。 最近我们发现SIF因子与干扰素有关。 可诱导的P91转录因子。这项提案的目标将是 了解PDGF如何调节SIF和p9l，以及它们扮演什么角色 参与c-fos原癌基因的调控。我们的具体目标将是 (1)鉴定和分析P91的功能结构域；(2) 鉴定和克隆组成SIF复合体的其他蛋白质；(3) 确定p9l在c-fos启动子调控中的作用 PDGF和干扰素。 最近发现p9l或相关蛋白具有重要作用。 在多种生长因子的信号传导中发挥作用 细胞因子。这些研究的结果将加深我们对 这条主要的信号转导途径。

One of the major questions in cell biology and cancer research is how are signals transduced from the surface of the cell to the nucleus to regulate specific gene expression. Previously my laboratory has identified a PDGF inducible factor called SIF which is involved in the regulation of the c- fos proto-oncogene. The SIF factor has a rapidly inducible DNA binding activity that is activated in the absence of new protein synthesis. It is a candidate for being a direct intermediary between the cell surface and the nucleus. Ourselves and others have shown that this factor can respond not only to PDGF, but other polypeptide growth factors such as EGF, insulin, and CSF- l. Recently we have shown that the SIF factor is related to the interferon inducible p91 transcription factor. The goal of this proposal will be to understand how SIF and p9l are regulated by PDGF and what role do they play in the regulation of the c-fos proto-oncogene. Our specific aims will be to (I) identify and analyze the functional domains of p91; (2) to identify and clone other proteins that make up the SIF complexes and; (3) to determine the role of p9l in the regulation of the c-fos promoter by PDGF and interferon. It has recently been found that p9l or related proteins have major roles to play in the signal transduction of a variety of growth factors and cytokines. The results of these studies will enhance our understanding of this major signal transduction pathway.