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， 从细胞表面传导到细胞核的信号， 特异性基因表达之前我的实验室已经鉴定出一种PDGF 诱导因子称为SIF，其参与c- fos原癌基因SIF因子具有快速诱导的DNA结合 在没有新蛋白质合成的情况下被激活的活性。是 作为细胞表面和细胞膜之间的直接媒介的候选物， 原子核我们自己和其他人已经证明， 不仅是PDGF，还有其它多肽生长因子如EGF， 胰岛素和CSF-I。 最近，我们发现SIF因子与干扰素有关， 诱导型p91转录因子。本提案的目标是 了解SIF和p9 l是如何被PDGF调节的，以及它们 在c-fos原癌基因的调节中起作用。我们的具体目标将 （1）鉴定和分析p91的功能结构域;（2） 鉴定和克隆构成SIF复合物的其他蛋白质;（3） 为了确定p9 L在c-fos启动子的调节中的作用， PDGF和干扰素。 最近发现，p9 l或相关蛋白具有重要作用， 在多种生长因子的信号转导中发挥作用， 细胞因子这些研究的结果将增进我们对 这个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.