The regulation of gene expression by growth factors is an essential part of the mitogenic process. We have previously identified a factor whose DNA binding activity is rapidly induced upon treatment of quiescent fibroblasts with sis/PDGF. The induction of this factor occurs in the absence of protein synthesis, and therefore it is likely to be part of the signal transduction pathway which leads from the PDGF receptor to the nucleus. This factor binds to a conserved sequence 346 bp upstream of the c-fos proto-oncogene promoter and is distinct form factors which interact with the c-fos serum response element. This sis-inducible factor (SIF) responds specifically to sis/PDGF treatment of quiescent fibroblasts, and is not at all or only weakly activated by serum or phorbol esters. The SIF binding recognition element is sufficient to confer sis-inducibility onto a truncated c-fos promoter seeks to further characterize the SIF factor. The goals of this proposal can be summarized as five broad specific aims: 1. To identify elements which cooperate with the SIF element to confer PDGF inducibility. 2. To obtain identify and characterize cDNA clones of the SIF gene. 3. To determine the molecular basis for the induction of SIF DNA-binding activity by sis/PDGF. 4. To determine the domains of the SIF protein responsible for DNA-binding and transcriptional activation. 5. To characterize the developmental and tissue-specific distribution of SIF expression. Results obtained from these studies will greatly enhance our understanding of growth factor action, signal transduction, and cancer.
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