Proteomic Techniques For Altering Cellular Function

Not all manipulations of gene products are made at the gene level. It is possible to modify cell function by interfering directly with gene products (i.e., the proteomic strategy). One mechanism for such manipulation involves adding peptides that correspond to the active regions of proteins. These peptides bind to the molecular targets of those proteins within the cell and block the downstream effects. Sometimes these peptides can mimic the effect of the larger peptide. For example, a peptide corresponding to the carboxyl-terminal region of a G protein (which interacts with G protein-coupled receptors) was used to block the interaction between receptors and G proteins while "mimicking" the G protein to shift the receptor into a "high affinity" agonist-binding state (Rasenick et al. 1994). Although this strategy usually involves adding peptides to cells made permeable with a detergent or with electric current, it is also possible to incorporate DNA plasmids encoding peptides into cells (Gilchrist et al. 1999).

Another proteomic strategy for manipulating cellular processes involves expression of "dominant-negative" proteins that are generated in sufficient amount to block the activity of the native protein in the cell. Usually this strategy involves the construction of a mutant protein that is similar to the protein of interest but deficient at some active site. This inactive mutant protein, expressed in considerable excess over the native protein, competes with the native protein for target sites and inhibits its activity (Osawa and Johnson 1991).

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