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.
| Kim, D W; Cochran, B H (2001) JAK2 activates TFII-I and regulates its interaction with extracellular signal-regulated kinase. Mol Cell Biol 21:3387-97 |
| Kim, D W; Cochran, B H (2000) Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter. Mol Cell Biol 20:1140-8 |
| Simon, A R; Rai, U; Fanburg, B L et al. (1998) Activation of the JAK-STAT pathway by reactive oxygen species. Am J Physiol 275:C1640-52 |
| Kim, D W; Cheriyath, V; Roy, A L et al. (1998) TFII-I enhances activation of the c-fos promoter through interactions with upstream elements. Mol Cell Biol 18:3310-20 |
