Chemical dimerizers and three-hybrid systems: scanning the proteome for targets of organic small molecules.

The integration of technological advances in areas as diverse as chemical biology, proteomics, genomics, automation, and bioinformatics has led to the emergence of novel screening paradigms for analyzing the molecular basis of drug action. This review summarizes recent advances in three-hybrid technologies and their application to the characterization of small molecule-protein interactions and proteome-wide identification of drug receptors.

[1]  S. Fields,et al.  Protein-peptide interactions analyzed with the yeast two-hybrid system. , 1995, Nucleic acids research.

[2]  H. Ploegh,et al.  Chemistry-based functional proteomics reveals novel members of the deubiquitinating enzyme family. , 2002, Chemistry & biology.

[3]  B. Cravatt,et al.  Chemical Strategies for Functional Proteomics* , 2002, Molecular & Cellular Proteomics.

[4]  N. Lehming,et al.  A new method for the selection of protein interactions in mammalian cells. , 2000, The Biochemical journal.

[5]  S. Fields,et al.  Protein analysis on a proteomic scale , 2003, Nature.

[6]  Stephen H. Friend,et al.  Toxicogenomics and drug discovery: will new technologies help us produce better drugs? , 2002, Nature Reviews Drug Discovery.

[7]  T. Clackson,et al.  Regulated gene expression systems , 2000, Gene Therapy.

[8]  Stuart L. Schreiber,et al.  Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes , 1991, Cell.

[9]  T. Rabbitts,et al.  Selection of antibodies for intracellular function using a two-hybrid in vivo system. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[10]  S. Schreiber,et al.  Dimeric ligands define a role for transcriptional activation domains in reinitiation , 1996, Nature.

[11]  M. Vidal,et al.  Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  A. Galarneau,et al.  β-Lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein–protein interactions , 2002, Nature Biotechnology.

[13]  Peter G. Schultz,et al.  A chemical switch for inhibitor-sensitive alleles of any protein kinase , 2000, Nature.

[14]  S. Schreiber,et al.  TGF-β-signaling with small molecule FKBP12 antagonists that bind myristoylated FKBP12-TGF-β type I receptor fusion proteins , 1998 .

[15]  Eric A. Althoff,et al.  Receptor‐Dependence of the Transcription Read‐Out in a Small‐Molecule Three‐Hybrid System , 2002, ChemBioChem.

[16]  D N Woolfson,et al.  A ligand-reversible dimerization system for controlling protein-protein interactions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Verdine,et al.  A synthetic library of cell-permeable molecules. , 2001, Journal of the American Chemical Society.

[18]  S. Hanash.  Disease proteomics : Proteomics , 2003 .

[19]  Shannon R. Magari,et al.  A humanized system for pharmacologic control of gene expression , 1996, Nature Medicine.

[20]  R. Brent,et al.  Two classes of proteins dependent on either the presence or absence of thyroid hormone for interaction with the thyroid hormone receptor. , 1995, Molecular endocrinology.

[21]  Stephen J Benkovic,et al.  Using an AraC-based three-hybrid system to detect biocatalysts in vivo , 2000, Nature Biotechnology.

[22]  A. Varshavsky,et al.  Split ubiquitin as a sensor of protein interactions in vivo. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  B. Cravatt,et al.  Proteomic profiling of mechanistically distinct enzyme classes using a common chemotype , 2002, Nature Biotechnology.

[24]  W. Abida,et al.  Dexamethasone−Methotrexate: An Efficient Chemical Inducer of Protein Dimerization In Vivo , 2000 .

[25]  S. Schreiber,et al.  Mechanistic studies of a signaling pathway activated by the organic dimerizer FK1012. , 1994, Chemistry & biology.

[26]  S. Schreiber,et al.  Functional analysis of Fas signaling in vivo using synthetic inducers of dimerization , 1996, Current Biology.

[27]  Stanley Fields,et al.  The Two-Hybrid System , 2001 .

[28]  S. Schreiber,et al.  Small-molecule control of insulin and PDGF receptor signaling and the role of membrane attachment , 1998, Current Biology.

[29]  Sebastian Meier-Ewert,et al.  A three-hybrid approach to scanning the proteome for targets of small molecule kinase inhibitors. , 2004, Chemistry & biology.

[30]  Yudong D. He,et al.  Functional Discovery via a Compendium of Expression Profiles , 2000, Cell.

[31]  J. Kraut,et al.  Role of aspartate 27 in the binding of methotrexate to dihydrofolate reductase from Escherichia coli. , 1988, The Journal of biological chemistry.

[32]  S. Schreiber,et al.  A yeast genetic system for selecting small molecule inhibitors of protein-protein interactions in nanodroplets. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[33]  S. Schreiber,et al.  Probing the role of homomeric and heteromeric receptor interactions in TGF-β signaling using small molecule dimerizers , 1998, Current Biology.

[34]  L Orci,et al.  Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. , 2000, Science.

[35]  S. Schreiber.  Chemical genetics resulting from a passion for synthetic organic chemistry. , 1998, Bioorganic & medicinal chemistry.

[36]  R W King,et al.  Kinetics of substrate, coenzyme, and inhibitor binding to Escherichia coli dihydrofolate reductase. , 1981, Biochemistry.

[37]  S. Fields,et al.  The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Irwin D Kuntz,et al.  Small molecule affinity fingerprinting. A tool for enzyme family subclassification, target identification, and inhibitor design. , 2002, Chemistry & biology.

[39]  Raymond L. Blakley,et al.  Kinetics of the formation and isomerization of methotrexate complexes of recombinant human dihydrofolate reductase. , 1988, The Journal of biological chemistry.

[40]  Paul Tempst,et al.  RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs , 1994, Cell.

[41]  RAPT1, a mammalian homolog of yeast Tor, interacts with the FKBP12/rapamycin complex. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[42]  Stuart L. Schreiber,et al.  A mammalian protein targeted by G1-arresting rapamycin–receptor complex , 1994, Nature.

[43]  J Mottram,et al.  Intracellular targets of cyclin-dependent kinase inhibitors: identification by affinity chromatography using immobilised inhibitors. , 2000, Chemistry & biology.

[44]  Jie Zhang,et al.  Inhibitors of Ras/Raf-1 interaction identified by two-hybrid screening revert Ras-dependent transformation phenotypes in human cancer cells , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[45]  A. Jaxa-Chamiec,et al.  A GAL4-based yeast three-hybrid system for the identification of small molecule-target protein interactions. , 2002, Biochemical pharmacology.

[46]  P. J. Belshaw,et al.  Oligomerization activates c-Raf-1 through a Ras-dependent mechanism , 1996, Nature.

[47]  H. Blau,et al.  Protein–protein interactions monitored in mammalian cells via complementation of β-lactamase enzyme fragments , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[48]  M. Wickens,et al.  A three-hybrid system to detect RNA-protein interactions in vivo. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[49]  J. Heitman,et al.  Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast , 1991, Science.

[50]  T. Clackson,et al.  Dimerizer-regulated gene expression. , 2002, Current opinion in biotechnology.

[51]  T. Clackson,et al.  Regulation of endogenous gene expression with a small-molecule dimerizer , 2002, Nature Biotechnology.

[52]  A. Burlingame,et al.  Chemical Approaches for Functionally Probing the Proteome* , 2002, Molecular & Cellular Proteomics.

[53]  S. Schreiber,et al.  Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[54]  D. Baccanari,et al.  Dihydrofolate reductase hysteresis and its effect of inhibitor binding analyses. , 1981, Biochemistry.

[55]  D. Baccanari,et al.  Inhibition of dihydrofolate reductase: effect of reduced nicotinamide adenine dinucleotide phosphate on the selectivity and affinity of diaminobenzylpyrimidines. , 1982, Biochemistry.

[56]  V. Cornish,et al.  Chemical complementation: A reaction-independent genetic assay for enzyme catalysis , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[57]  S. Michnick,et al.  Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[58]  K. Peterson,et al.  A proliferation switch for genetically modified cells. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[59]  Jan Tavernier,et al.  Design and application of a cytokine-receptor-based interaction trap , 2001, Nature Cell Biology.

[60]  H. Hidaka,et al.  Isolation of cDNAs encoding cellular drug-binding proteins using a novel expression cloning procedure: drug-western. , 1999, Molecular pharmacology.

[61]  S. Frye.  Structure-activity relationship homology (SARAH): a conceptual framework for drug discovery in the genomic era. , 1999, Chemistry & biology.

[62]  D. Austin,et al.  Display cloning: functional identification of natural product receptors using cDNA-phage display. , 1999, Chemistry & biology.

[63]  T. Clackson,et al.  Delivery of a stringent dimerizer-regulated gene expression system in a single retroviral vector. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[64]  E J Licitra,et al.  A three-hybrid system for detecting small ligand-protein receptor interactions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[65]  D. Holt,et al.  A versatile synthetic dimerizer for the regulation of protein-protein interactions. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[66]  B. Kreider,et al.  Drug receptor identification from multiple tissues using cellular-derived mRNA display libraries. , 2002, Chemistry & biology.

[67]  Shannon R. Magari,et al.  Redesigning an FKBP-ligand interface to generate chemical dimerizers with novel specificity. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[68]  P. Brown,et al.  Drug target validation and identification of secondary drug target effects using DNA microarrays , 1998, Nature Medicine.

[69]  S. Schreiber,et al.  Signal transduction in T lymphocytes using a conditional allele of Sos. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[70]  J. Waring,et al.  The impact of genomics-based technologies on drug safety evaluation. , 2000, Annual review of pharmacology and toxicology.

[71]  S. Schreiber,et al.  Controlling signal transduction with synthetic ligands. , 1993, Science.

[72]  S. Schreiber,et al.  A general strategy for producing conditional alleles of Src-like tyrosine kinases. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[73]  S. Schreiber,et al.  Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[74]  D. Moore,et al.  A chimeric thyroid hormone receptor constitutively bound to DNA requires retinoid X receptor for hormone-dependent transcriptional activation in yeast. , 1994, Molecular endocrinology.

[75]  K. Resing,et al.  Identification of novel MAP kinase pathway signaling targets by functional proteomics and mass spectrometry. , 2000, Molecular cell.

[76]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[77]  S. Schreiber,et al.  Controlling programmed cell death with a cyclophilin-cyclosporin-based chemical inducer of dimerization. , 1996, Chemistry & biology.

[78]  B. Stockwell,et al.  Frontiers in chemical genetics. , 2000, Trends in biotechnology.

[79]  V. Cornish,et al.  An optimized dexamethasone-methotrexate yeast 3-hybrid system for high-throughput screening of small molecule-protein interactions. , 2003, Analytical biochemistry.