DROSOPHILA MYC IS ONCOGENIC IN MAMMALIAN-CELLS AND PLAYS A ROLE IN THE DIMINUTIVE PHENOTYPE

Biochemical and biological activities of Myc oncoproteins are highly d ependent upon their association with another basic region helix-loop-h elix/leucine zipper (bHLH/LZ) protein, Max. Our previous observation t hat the DNA-binding/dimerization region of Max is absolutely conserved throughout vertebrate evolution provided the basis for a yeast two-hy brid interaction screen that led to the isolation of the Drosophila My c (dMyc1) protein. Structural conservation in regions of known functio nal significance is consistent with the ability of dMyc1 to interact w ith vertebrate Max, to transactivate gene expression in yeast cells, a nd to cooperate with activated H-RAS to effect the malignant transform ation of primary mammalian cells. The ability of P-element-mediated ec topic expression of dmyc1 to reverse a subset of the phenotypic altera tions associated with the diminutive mutation suggests that diminutive may correspond to dmyc1. This finding, along with the localization of dmyc1 expression to zones of high proliferative activity in the embry o, implicates dMyc1 as an integral regulator of Drosophila growth and development.