Genetic selection of growth-inhibitory sequences in mammalian cells

To assess the role of mitogenically activated genes in the control of cell proliferation, we have taken a genetic approach based on the premise that blocking the function of an essential gene should lead to growth inhibition. Using a newly developed selection procedure, we isolated growth-inhibitory sequences from a pool of random cDNA fragments of 19 growth-related genes associated with the G₀/G₁ transition. These sequences encode potential dominant negative variants of c-Fos, JunB, and p44(MAPK) that may interfere with their growth-related functions. We anticipate that this procedure, which allows for the selection of sequences that cause a growth-inhibition phenotype, may have broad applications in the identification and analysis of genes that regulate cell growth.