title: Detection of peptides, proteins, and drugs that selectively interact with protein targets.
abstract: Genome sequencing has been completed for multiple organisms, and pilot proteomic analyses reported for yeast and higher eukaryotes. This work has emphasized the facts that proteins are frequently engaged in multiple interactions, and that governance of protein interaction specificity is a primary means of regulating biological systems. In particular, the ability to deconvolute complex protein interaction networks to identify which interactions govern specific signaling pathways requires the generation of biological tools that allow the distinction of critical from noncritical interactions. We report the application of an enhanced Dual Bait two-hybrid system to allow detection and manipulation of highly specific protein-protein interactions. We summarize the use of this system to detect proteins and peptides that target well-defined specific motifs in larger protein structures, to facilitate rapid identification of specific interactors from a pool of putative interacting proteins obtained in a library screen, and to score specific drug-mediated disruption of protein-protein interaction.
authors.affiliation: Division of Basic Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA.
authors.forename: Ilya G
authors.initials: IG
authors.lastname: Serebriiskii
authors.forename: Olga
authors.initials: O
authors.lastname: Mitina
authors.forename: Elena N
authors.initials: EN
authors.lastname: Pugacheva
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Benevolenskaya
authors.forename: Elena
authors.initials: E
authors.lastname: Kotova
authors.forename: Garabet G
authors.initials: GG
authors.lastname: Toby
authors.forename: Vladimir
authors.initials: V
authors.lastname: Khazak
authors.forename: William G
authors.initials: WG
authors.lastname: Kaelin
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chernoff
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D003001:Cloning, Molecular; D030562:Databases, Protein; D016678:Genome; D016681:Genome, Fungal; D015894:Genome, Human; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020543:Proteome / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C099942:NEDD9 protein, human; D010455:Peptides; D004364:Pharmaceutical Preparations; D010750:Phosphoproteins; D011506:Proteins; D020543:Proteome; D016160:Retinoblastoma Protein; D020846:cdc42 GTP-Binding Protein, Saccharomyces cerevisiae