MOLECULAR CLONING OF C-MYC TRANSCRIPTION FACTOR GENES

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Dr. Victor Lobanenkov, is experienced in identifying and characterizing trans-acting transcription factors. He plans to collaborate with Dr. Paul Neiman to exploit the biological systems Dr. Neiman has characterized, namely the development and differentiation of avian B-cells in the bursa of Fabricius in which the controlled expression of the c-myc proto-oncogene plays an important role. We plan to identify the regulatory factors which are involved in regulating initiation and/or elongation of the transcription of the c-myc gene with the major emphasis toward understanding how these control the gene in bursal B-cells. Having identified the DNA-binding proteins involved, the cDNAs encoding these proteins will be isolated. These cDNAs will be used to study expression of the genes in B-cells and retrovirus vectors will be used to reintroduce the' genes into B-cells, either as constitutively active factors or as "dominant negative" factors, to investigate their effects on B-cell development. The cloned genes will also be used to express the proteins in E. coli for studies of protein interaction. As part of the research program, we wish to identify cis and trans elements involved in myc negative autoregulation. To this end, we plan to use a recently developed approach based on retrovirus construct transducing both expression of the conditional myc-fusion protein and a selectable marker.