The regulational of transcription of structural eukaryotic genes appears to involve the direction of RNA polymerase II to the promoter region by sequence specific DNA binding proteins. Studies of the SV40 as well as other viral and cellular promoters have defined a GC rich consensus sequence which bidirectionally stimulates transcription. The cellular factor SP1 binds to this region and in SV40 stimulates early viral RNA production whicle this laboratory has characterized another cellular protein (LSF) which binds the same sequences yet stimulates late transcription. The mechanism of action of these proteins is completely unknown. Such factors are extraordinarily rare and purification yields minute quantities; therefore further studies will necessitate cloning the genes for LSF and SP1. Novel techniques of screening a lambda gt-11 expression library will be attempted taking advantage of the specific DNA binding capabilities of the factors. Clones thus obtained will be used to construct full length cDNAs. These will be used as probes of the in vivo functions of LSF and SP1 during the cell cycle, transformation and SV40 infection. Such cDNAs could be used in mammalian expression systems so as to overproduce transcription factors whose interactions with DNA, RNA polymerase II and other proteins could be analyzed in vitro.
| Hanna-Rose, W; Licht, J D; Hansen, U (1997) Two evolutionarily conserved repression domains in the Drosophila Kruppel protein differ in activator specificity. Mol Cell Biol 17:4820-9 |
| Licht, J D; Hanna-Rose, W; Reddy, J C et al. (1994) Mapping and mutagenesis of the amino-terminal transcriptional repression domain of the Drosophila Kruppel protein. Mol Cell Biol 14:4057-66 |
| DeFranco, C; Ro, M; Grossel, M et al. (1993) NGFIA (EGR1) contains transcription activating domains in both the amino terminal and carboxyl terminal regions of the protein. Biochem Biophys Res Commun 194:425-31 |
| Licht, J D; Ro, M; English, M A et al. (1993) Selective repression of transcriptional activators at a distance by the Drosophila Kruppel protein. Proc Natl Acad Sci U S A 90:11361-5 |
| Licht, J D; Bosserman, L D; Andersen, J W et al. (1990) Treatment of low-grade and intermediate-grade lymphoma with intensive combination chemotherapy results in long-term, disease-free survival. Cancer 66:632-9 |
