메뉴 건너뛰기




Volumn 13, Issue 5, 2002, Pages 459-467

Dimerizer-regulated gene expression

Author keywords

[No Author keywords available]

Indexed keywords

ADENOVIRUS VECTOR; DEXAMETHASONE; METHOTREXATE; TACROLIMUS; VIRUS VECTOR;

EID: 0036810868     PISSN: 09581669     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0958-1669(02)00373-7     Document Type: Review
Times cited : (95)

References (40)
  • 1
    • 0033981631 scopus 로고    scopus 로고
    • Regulated gene expression systems
    • Clackson T. Regulated gene expression systems. Gene Ther. 7:2000;120-125.
    • (2000) Gene Ther , vol.7 , pp. 120-125
    • Clackson, T.1
  • 2
    • 0031197176 scopus 로고    scopus 로고
    • Controlling mammalian gene expression with small molecules
    • Clackson T. Controlling mammalian gene expression with small molecules. Curr Opin Chem Biol. 1:1997;210-218.
    • (1997) Curr Opin Chem Biol , vol.1 , pp. 210-218
    • Clackson, T.1
  • 3
    • 0032192146 scopus 로고    scopus 로고
    • Recent advances in inducible gene expression systems
    • Rossi F.M., Blau H.M. Recent advances in inducible gene expression systems. Curr Opin Biotechnol. 9:1998;451-456.
    • (1998) Curr Opin Biotechnol , vol.9 , pp. 451-456
    • Rossi, F.M.1    Blau, H.M.2
  • 4
    • 0029737867 scopus 로고    scopus 로고
    • Dimeric ligands define a role for transcriptional activation domains in reinitiation
    • Ho S.N., Biggar S.R., Spencer D.M., Schreiber S.L., Crabtree G.R. Dimeric ligands define a role for transcriptional activation domains in reinitiation. Nature. 382:1996;822-826.
    • (1996) Nature , vol.382 , pp. 822-826
    • Ho, S.N.1    Biggar, S.R.2    Spencer, D.M.3    Schreiber, S.L.4    Crabtree, G.R.5
  • 6
    • 0032790270 scopus 로고    scopus 로고
    • Regulation of gene expression with synthetic dimerizers
    • Pollock R., Rivera V.M. Regulation of gene expression with synthetic dimerizers. Methods Enzymol. 306:1999;263-281.
    • (1999) Methods Enzymol , vol.306 , pp. 263-281
    • Pollock, R.1    Rivera, V.M.2
  • 7
    • 0031833563 scopus 로고    scopus 로고
    • Mammalian target of rapamycin: Immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling
    • Abraham R.T. Mammalian target of rapamycin: immunosuppressive drugs uncover a novel pathway of cytokine receptor signaling. Curr Opin Immunol. 10:1998;330-336.
    • (1998) Curr Opin Immunol , vol.10 , pp. 330-336
    • Abraham, R.T.1
  • 10
    • 0034881393 scopus 로고    scopus 로고
    • Sirolimus, but not the structurally related RAD (everolimus), enhances the negative effects of cyclosporine on mitochondrial metabolism in the rat brain
    • Serkova N., Jacobsen W., Niemann C.U., Litt L., Benet L.Z., Leibfritz D., Christians U. Sirolimus, but not the structurally related RAD (everolimus), enhances the negative effects of cyclosporine on mitochondrial metabolism in the rat brain. Br J Pharmacol. 133:2001;875-885.
    • (2001) Br J Pharmacol , vol.133 , pp. 875-885
    • Serkova, N.1    Jacobsen, W.2    Niemann, C.U.3    Litt, L.4    Benet, L.Z.5    Leibfritz, D.6    Christians, U.7
  • 11
    • 0028948325 scopus 로고
    • Structure-based design of transcription factors
    • Pomerantz J.L., Sharp P.A., Pabo C.O. Structure-based design of transcription factors. Science. 267:1995;93-96.
    • (1995) Science , vol.267 , pp. 93-96
    • Pomerantz, J.L.1    Sharp, P.A.2    Pabo, C.O.3
  • 12
    • 0031441285 scopus 로고    scopus 로고
    • Pharmacologic control of a humanized gene therapy system implanted into nude mice
    • Magari S.R., Rivera V.M., Iuliucci J.D., Gilman M., Cerasoli F. Jr. Pharmacologic control of a humanized gene therapy system implanted into nude mice. J Clin Invest. 100:1997;2865-2872.
    • (1997) J Clin Invest , vol.100 , pp. 2865-2872
    • Magari, S.R.1    Rivera, V.M.2    Iuliucci, J.D.3    Gilman, M.4    Cerasoli F., Jr.5
  • 13
    • 0034700090 scopus 로고    scopus 로고
    • Delivery of a stringent dimerizer-regulated gene expression system in a single retroviral vector
    • Pollock R., Issner R., Zoller K., Natesan S., Rivera V.M., Clackson T. Delivery of a stringent dimerizer-regulated gene expression system in a single retroviral vector. Proc Natl Acad Sci USA. 97:2000;13221-13226.
    • (2000) Proc Natl Acad Sci USA , vol.97 , pp. 13221-13226
    • Pollock, R.1    Issner, R.2    Zoller, K.3    Natesan, S.4    Rivera, V.M.5    Clackson, T.6
  • 14
  • 15
    • 0030878873 scopus 로고    scopus 로고
    • Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen
    • Liberles S.D., Diver S.T., Austin D.J., Schreiber S.L. Inducible gene expression and protein translocation using nontoxic ligands identified by a mammalian three-hybrid screen. Proc Natl Acad Sci USA. 94:1997;7825-7830.
    • (1997) Proc Natl Acad Sci USA , vol.94 , pp. 7825-7830
    • Liberles, S.D.1    Diver, S.T.2    Austin, D.J.3    Schreiber, S.L.4
  • 17
    • 0034890962 scopus 로고    scopus 로고
    • Regulated gene expression in glioma cells: A comparison of three inducible systems
    • Senner V., Sotoodeh A., Paulus W. Regulated gene expression in glioma cells: a comparison of three inducible systems. Neurochem Res. 26:2001;521-524. This article compares the early generation AP1510-based homodimerizer system with the Tet-off and ecdysone systems in transiently transfected rat C6 glioma cells. The dimerizer system was found to have the lowest basal levels of transcription and the highest induction ratios, but both the ecdysone and Tet-off systems supported higher levels of induced transcription. The AP1510-based system has now been superceded by the more effective rapamycin heterodimerizer system shown in Fig. 2.
    • (2001) Neurochem Res , vol.26 , pp. 521-524
    • Senner, V.1    Sotoodeh, A.2    Paulus, W.3
  • 18
    • 0036579880 scopus 로고    scopus 로고
    • Optimization and direct comparison of the dimerizer and reverse tet transcriptional control systems
    • Go W.Y., Ho S.N. Optimization and direct comparison of the dimerizer and reverse tet transcriptional control systems. J Gene Med. 4:2002;258-270. The authors compare a version of the rapamycin heterodimerizer system with an optimized Tet-on system in transient transfection assays in the Jurkat and NIH 3T3 cell lines. In an effort to eliminate all variables, transactivators were produced from identical expression vectors, contained the same activation domains, and were assayed on target promoters differing only in the transactivator DNA-binding sites. The Tet-on system gave the highest levels of induced transcription, but was 'leakier' than the dimerizer system. The authors conclude that the Tet-on system is suited to applications where high levels of target gene induction are required, whereas the dimerizer system is most useful where tight regulation is the priority. Note that the dimerizer system in this study used the Gal4 DBD in place of ZFHD1. Given that the Gal4-FKBP DBD fusion was found to non-specifically repress transcription when expressed at high levels, it is possible that this change reduced levels of target gene induction.
    • (2002) J Gene Med , vol.4 , pp. 258-270
    • Go, W.Y.1    Ho, S.N.2
  • 20
    • 0035989652 scopus 로고    scopus 로고
    • Regulation of endogenous gene expression with a small-molecule dimerizer
    • The authors replace ZFHD1 with an artificial zinc finger DBD targeting the human chromosomal VEGF gene promoter and demonstrate that the dimerizer system can be used to regulate the endogenous VEGF gene. Addition of a non-immunosuppressive C7-modified rapalog to cells transiently or stably transfected with the dimerizer-regulated zinc finger activator led to rapid, tight and dose-responsive induction of multiple VEGF splice variants to levels several fold higher than the natural hypoxic response. This is the first example of endogenous gene regulation via a designed zinc finger protein whose activity is under direct small-molecule control.
    • Pollock R., Giel M., Linher K., Clackson T. Regulation of endogenous gene expression with a small-molecule dimerizer. Nat Biotechnol. 20:2002;729-733. The authors replace ZFHD1 with an artificial zinc finger DBD targeting the human chromosomal VEGF gene promoter and demonstrate that the dimerizer system can be used to regulate the endogenous VEGF gene. Addition of a non-immunosuppressive C7-modified rapalog to cells transiently or stably transfected with the dimerizer-regulated zinc finger activator led to rapid, tight and dose-responsive induction of multiple VEGF splice variants to levels several fold higher than the natural hypoxic response. This is the first example of endogenous gene regulation via a designed zinc finger protein whose activity is under direct small-molecule control.
    • (2002) Nat Biotechnol , vol.20 , pp. 729-733
    • Pollock, R.1    Giel, M.2    Linher, K.3    Clackson, T.4
  • 21
    • 0033571527 scopus 로고    scopus 로고
    • Proteasome-mediated degradation of transcriptional activators correlates with activation domain potency in vivo
    • Molinari E., Gilman M., Natesan S. Proteasome-mediated degradation of transcriptional activators correlates with activation domain potency in vivo. EMBO J. 18:1999;6439-6447.
    • (1999) EMBO J , vol.18 , pp. 6439-6447
    • Molinari, E.1    Gilman, M.2    Natesan, S.3
  • 22
    • 0036168937 scopus 로고    scopus 로고
    • Engineering polydactyl zinc-finger transcription factors
    • Beerli R.R., Barbas C.F. I.I.I. Engineering polydactyl zinc-finger transcription factors. Nat Biotechnol. 20:2002;135-141.
    • (2002) Nat Biotechnol , vol.20 , pp. 135-141
    • Beerli, R.R.1    Barbas C.F., I.I.I.2
  • 24
    • 0034682787 scopus 로고    scopus 로고
    • Chemically regulated transcription factors reveal the persistence of repressor-resistant transcription after disrupting activator function
    • Biggar S.R., Crabtree G.R. Chemically regulated transcription factors reveal the persistence of repressor-resistant transcription after disrupting activator function. J Biol Chem. 275:2000;25381-25390.
    • (2000) J Biol Chem , vol.275 , pp. 25381-25390
    • Biggar, S.R.1    Crabtree, G.R.2
  • 25
    • 0035875668 scopus 로고    scopus 로고
    • Cell signaling can direct either binary or graded transcriptional responses
    • Biggar S.R., Crabtree G.R. Cell signaling can direct either binary or graded transcriptional responses. EMBO J. 20:2001;3167-3176.
    • (2001) EMBO J , vol.20 , pp. 3167-3176
    • Biggar, S.R.1    Crabtree, G.R.2
  • 26
    • 0036008098 scopus 로고    scopus 로고
    • Synthesis of calcineurin-resistant derivatives of FK506 and selection of compensatory receptors
    • A study combining structure-based design, synthetic chemistry and genetics to generate a dimerizer system that responds to non-immunosuppressive analogs of FK506. Using the crystal structure of the FKBP-FK506-CnA-B complex as a guide, a single-chain calcineurin A/B fusion (mCAB) was created that can bind FKBP-FK506. Non-immunosuppressive FK506 analogs were designed by modifying the C40 position and destroying calcineurin binding affinity. A yeast three-hybrid selection system was then used to select mCABs that can bind to the analogs from a targeted randomized library. The resulting system could be used to obtain robust activation of a reported gene in transiently transfected mammalian (Jurkat) cells.
    • Clemons P.A., Gladstone B.G., Seth A., Chao E.D., Foley M.A., Schreiber S.L. Synthesis of calcineurin-resistant derivatives of FK506 and selection of compensatory receptors. Chem Biol. 9:2002;49-61. A study combining structure-based design, synthetic chemistry and genetics to generate a dimerizer system that responds to non-immunosuppressive analogs of FK506. Using the crystal structure of the FKBP-FK506-CnA-B complex as a guide, a single-chain calcineurin A/B fusion (mCAB) was created that can bind FKBP-FK506. Non-immunosuppressive FK506 analogs were designed by modifying the C40 position and destroying calcineurin binding affinity. A yeast three-hybrid selection system was then used to select mCABs that can bind to the analogs from a targeted randomized library. The resulting system could be used to obtain robust activation of a reported gene in transiently transfected mammalian (Jurkat) cells.
    • (2002) Chem Biol , vol.9 , pp. 49-61
    • Clemons, P.A.1    Gladstone, B.G.2    Seth, A.3    Chao, E.D.4    Foley, M.A.5    Schreiber, S.L.6
  • 27
    • 0029824170 scopus 로고    scopus 로고
    • A three-hybrid system for detecting small ligand-protein receptor interactions
    • Licitra E.J., Liu J.O. A three-hybrid system for detecting small ligand-protein receptor interactions. Proc Natl Acad Sci USA. 93:1996;12817-12821.
    • (1996) Proc Natl Acad Sci USA , vol.93 , pp. 12817-12821
    • Licitra, E.J.1    Liu, J.O.2
  • 28
    • 0034600324 scopus 로고    scopus 로고
    • Dexamethasone-methotrexate: An efficient chemical inducer of dimerization in vivo
    • Lin H., Abida W.M., Sauer R.T., Cornish V.W. Dexamethasone-methotrexate: an efficient chemical inducer of dimerization in vivo. J Am Chem Soc. 122:2000;4247-4248.
    • (2000) J Am Chem Soc , vol.122 , pp. 4247-4248
    • Lin, H.1    Abida, W.M.2    Sauer, R.T.3    Cornish, V.W.4
  • 29
    • 0037007835 scopus 로고    scopus 로고
    • A bacterial small-molecule three-hybrid system
    • Describes the development of a new heterodimerizer, methotrexate-SLF, for use in three-hybrid assays. Methotrexate binds to glucocorticoid receptor domains; SLF is a synthetic ligand for FKBP and is the monomeric subunit of AP1510. The dimerizer is used to set up a bacterial three-hybrid system in which inducible transcription is obtained in Escherichia coli by fusing FKBP to the λcI DBD and fusing DHFR to a portion of the α-subunit of RNA polymerase.
    • Althoff E.A., Cornish V.W. A bacterial small-molecule three-hybrid system. Angew Chem Int Ed Engl. 41:2002;2327-2330. Describes the development of a new heterodimerizer, methotrexate-SLF, for use in three-hybrid assays. Methotrexate binds to glucocorticoid receptor domains; SLF is a synthetic ligand for FKBP and is the monomeric subunit of AP1510. The dimerizer is used to set up a bacterial three-hybrid system in which inducible transcription is obtained in Escherichia coli by fusing FKBP to the λcI DBD and fusing DHFR to a portion of the α-subunit of RNA polymerase.
    • (2002) Angew Chem Int Ed Engl , vol.41 , pp. 2327-2330
    • Althoff, E.A.1    Cornish, V.W.2
  • 30
    • 0036664935 scopus 로고    scopus 로고
    • Pharmacological regulation of protein expression from adeno-associated viral vectors in the eye
    • Describes the use of the optimized rapamycin system to achieve inducible protein expression in the eyes of rats and primates. Two AAV vectors, one expressing the transcription factors and the other harboring an EPO target gene, were co-injected in a 1:1 ratio into the subretinal space of rat eyes and EPO levels in the anterior chamber were measured. Expression before induction was negligible, but administration of systemic rapamycin provoked dose-dependent and reversible inductions of EPO. Peak expression levels were higher than those obtained following injection of equivalent doses of vectors in which EPO was expressed from the constitutive CMV promoter. Similar results were also obtained in a single non-human primate.
    • Auricchio A., Rivera V., Clackson T., O'Connor E., Maguire A., Tolentino M., Bennett J., Wilson J. Pharmacological regulation of protein expression from adeno-associated viral vectors in the eye. Mol Ther. 6:2002;238. Describes the use of the optimized rapamycin system to achieve inducible protein expression in the eyes of rats and primates. Two AAV vectors, one expressing the transcription factors and the other harboring an EPO target gene, were co-injected in a 1:1 ratio into the subretinal space of rat eyes and EPO levels in the anterior chamber were measured. Expression before induction was negligible, but administration of systemic rapamycin provoked dose-dependent and reversible inductions of EPO. Peak expression levels were higher than those obtained following injection of equivalent doses of vectors in which EPO was expressed from the constitutive CMV promoter. Similar results were also obtained in a single non-human primate.
    • (2002) Mol Ther , vol.6 , pp. 238
    • Auricchio, A.1    Rivera, V.2    Clackson, T.3    O'Connor, E.4    Maguire, A.5    Tolentino, M.6    Bennett, J.7    Wilson, J.8
  • 31
    • 0036169663 scopus 로고    scopus 로고
    • A system for small-molecule control of conditionally replication-competent adenoviral vectors
    • The rapamycin system is used to create an adenoviral vector whose replication can be induced pharmacologically. The E1 adenoviral genes that are critical for replication were placed downstream of the Z12 inducible promoter in an adenoviral vector. In cells co-infected with this vector and one expressing rapamycin-regulated transcription factors, viral titers could be increased by several orders of magnitude in response to a C7-modified rapalog; expression of a GM-CSF (granulocyte macrophage colony-stimulating factor) transgene on a third, replication-defective vector could also be induced. Similar results were obtained when the vectors were co-injected into tumor xenografts in mice.
    • Chong H., Ruchatz A., Clackson T., Rivera V.M., Vile R.G. A system for small-molecule control of conditionally replication-competent adenoviral vectors. Mol Ther. 5:2002;195-203. The rapamycin system is used to create an adenoviral vector whose replication can be induced pharmacologically. The E1 adenoviral genes that are critical for replication were placed downstream of the Z12 inducible promoter in an adenoviral vector. In cells co-infected with this vector and one expressing rapamycin-regulated transcription factors, viral titers could be increased by several orders of magnitude in response to a C7-modified rapalog; expression of a GM-CSF (granulocyte macrophage colony-stimulating factor) transgene on a third, replication-defective vector could also be induced. Similar results were obtained when the vectors were co-injected into tumor xenografts in mice.
    • (2002) Mol Ther , vol.5 , pp. 195-203
    • Chong, H.1    Ruchatz, A.2    Clackson, T.3    Rivera, V.M.4    Vile, R.G.5
  • 32
    • 0036328505 scopus 로고    scopus 로고
    • Constitutive and regulated expression of processed insulin following in vivo hepatic gene transfer
    • The optimized rapamycin system is used to achieve inducible expression of insulin from mouse liver following adenoviral gene transfer. The system is again introduced using a two-vector approach. A series of modified proinsulin constructs are assessed in which removal of the C peptide (to liberate active insulin) can potentially be achieved by endogenously expressed proteases, with a furin-cleavable construct being the best. Tight, inducible expression of insulin is demonstrated, resulting in transient changes in blood glucose. Although the kinetics of transcriptional regulation may not be ideal for rapidly modulating blood glucose levels, this system might offer a viable alternative to administration of long-acting insulin for treatment of type I diabetes.
    • Auricchio A., Gao G.P., Yu Q.C., Raper S., Rivera V.M., Clackson T., Wilson J.M. Constitutive and regulated expression of processed insulin following in vivo hepatic gene transfer. Gene Ther. 9:2002;963-971. The optimized rapamycin system is used to achieve inducible expression of insulin from mouse liver following adenoviral gene transfer. The system is again introduced using a two-vector approach. A series of modified proinsulin constructs are assessed in which removal of the C peptide (to liberate active insulin) can potentially be achieved by endogenously expressed proteases, with a furin-cleavable construct being the best. Tight, inducible expression of insulin is demonstrated, resulting in transient changes in blood glucose. Although the kinetics of transcriptional regulation may not be ideal for rapidly modulating blood glucose levels, this system might offer a viable alternative to administration of long-acting insulin for treatment of type I diabetes.
    • (2002) Gene Ther , vol.9 , pp. 963-971
    • Auricchio, A.1    Gao, G.P.2    Yu, Q.C.3    Raper, S.4    Rivera, V.M.5    Clackson, T.6    Wilson, J.M.7
  • 33
    • 0011625753 scopus 로고    scopus 로고
    • Development of regulated lentiviral vectors
    • Luce M.J., Reiser J. Development of regulated lentiviral vectors. Mol Ther. 5:2002;S32.
    • (2002) Mol Ther , vol.5 , pp. 32
    • Luce, M.J.1    Reiser, J.2
  • 34
    • 0011626023 scopus 로고    scopus 로고
    • Drug-regulated gene expression in post-mitotic cells using amplicon vectors
    • Wang S., Petravicz J., Breakefield X. Drug-regulated gene expression in post-mitotic cells using amplicon vectors. Mol Ther. 3:2001;S400.
    • (2001) Mol Ther , vol.3 , pp. 400
    • Wang, S.1    Petravicz, J.2    Breakefield, X.3
  • 35
    • 0011687232 scopus 로고    scopus 로고
    • Regulated delivery of secreted proteins following hydrodynamic delivery of DNA to mice
    • Rivera V.M., Wardwell S., Tang H., Wang X., Clackson T. Regulated delivery of secreted proteins following hydrodynamic delivery of DNA to mice. Mol Ther. 5:2002;S325.
    • (2002) Mol Ther , vol.5 , pp. 325
    • Rivera, V.M.1    Wardwell, S.2    Tang, H.3    Wang, X.4    Clackson, T.5
  • 36
    • 0030911791 scopus 로고    scopus 로고
    • Transcriptional control in keratinocytes and fibroblasts using synthetic ligands
    • Freiberg R.A., Ho S.N., Khavari P.A. Transcriptional control in keratinocytes and fibroblasts using synthetic ligands. J Clin Invest. 99:1997;2610-2615.
    • (1997) J Clin Invest , vol.99 , pp. 2610-2615
    • Freiberg, R.A.1    Ho, S.N.2    Khavari, P.A.3
  • 37
    • 0030759476 scopus 로고    scopus 로고
    • Single-step synthesis of cell-permeable protein dimerizers that activate signal transduction and gene expression
    • Diver S.T., Schreiber S.L. Single-step synthesis of cell-permeable protein dimerizers that activate signal transduction and gene expression. J Am Chem Soc. 119:1997;5106-5109.
    • (1997) J Am Chem Soc , vol.119 , pp. 5106-5109
    • Diver, S.T.1    Schreiber, S.L.2
  • 38
    • 0031691987 scopus 로고    scopus 로고
    • Controlling gene expression using synthetic ligands
    • Rivera V.M. Controlling gene expression using synthetic ligands. Methods. 14:1998;421-429.
    • (1998) Methods , vol.14 , pp. 421-429
    • Rivera, V.M.1
  • 39
    • 0030013607 scopus 로고    scopus 로고
    • Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins
    • Belshaw P.J., Ho S.N., Crabtree G.R., Schreiber S.L. Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins. Proc Natl Acad Sci USA. 93:1996;4604-4607.
    • (1996) Proc Natl Acad Sci USA , vol.93 , pp. 4604-4607
    • Belshaw, P.J.1    Ho, S.N.2    Crabtree, G.R.3    Schreiber, S.L.4
  • 40
    • 0027960971 scopus 로고
    • Molecular analysis of the interaction of calcineurin with drug-immunophilin complexes
    • Clipstone N.A., Fiorentino D.F., Crabtree G.R. Molecular analysis of the interaction of calcineurin with drug-immunophilin complexes. J Biol Chem. 269:1994;26431-26437.
    • (1994) J Biol Chem , vol.269 , pp. 26431-26437
    • Clipstone, N.A.1    Fiorentino, D.F.2    Crabtree, G.R.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.