We have expressed libraries of peptides in mammalian cells to select for tr
ans-dominant effects on intracellular signaling systems. As an example-and
to reveal pharmacologically relevant points in pathways that lead to Taxol
resistance-we selected for peptide motifs that confer resistance to Taxol-i
nduced cell death. Of several peptides selected, one, termed RGP8.5, was li
nked to upregulation of expression of the gene ABCB1 (also known as MDR1, f
or multiple drug resistance) in HeLa cells. Our data indicate that trans-do
minant effector peptides can point to potential mechanisms by which signali
ng systems operate. Such tools may be useful in functional genomic analysis
of signaling pathways in mammalian disease processes.