![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 58, Issue 1, 1-10, July 2000
Department of Pharmacology, School of Medicine, University of North
Carolina, Chapel Hill, North Carolina
The ability to selectively regulate the expression of genes implicated
in cancer or other diseases could have important ramifications for both
basic research and for therapy. Using peptide combinatorial libraries
expressed in yeast, we have screened for novel zinc finger proteins
that selectively bind to an overlapping EGR1/SP1/WT1 regulatory site in
the promoter of the MDR1 multidrug resistance gene. The novel proteins
were only moderately effective in blocking transcription by simple
masking of the target site. However, when coupled to mammalian
transactivator or repressor domains, they could selectively modulate
the expression of reporter genes having promoters containing the MDR1
target site. Moreover, they could also regulate transcription of the
chromosomal MDR1 gene. Thus, in K562 cells,
12-O-tetradecanoylphorbol-13-acetate-inducible expression of P-glycoprotein, the product of MDR1 gene, was strongly and selectively inhibited by the presence of a repressor protein targeted to the MDR1 promoter. These studies potentially provide a
novel alternative approach to the control of multidrug resistance. They
also provide important insights into strategies for developing selective regulators of gene expression.
This article has been cited by other articles:
|
|
 |
|
  V. Dixit and R. L. Juliano Selective Killing of Smad4-Negative Tumor Cells via a Designed Repressor Strategy Mol. Pharmacol., July 1, 2008; 74(1): 289 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Durai, M. Mani, K. Kandavelou, J. Wu, M. H. Porteus, and S. Chandrasegaran Zinc finger nucleases: custom-designed molecular scissors for genome engineering of plant and mammalian cells Nucleic Acids Res., October 26, 2005; 33(18): 5978 - 5990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Juliano, V. R. Dixit, H. Kang, T. Y. Kim, Y. Miyamoto, and D. Xu Epigenetic manipulation of gene expression: a toolkit for cell biologists J. Cell Biol., June 20, 2005; 169(6): 847 - 857. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Blancafort, D. J. Segal, and C. F. Barbas III Designing Transcription Factor Architectures for Drug Discovery Mol. Pharmacol., December 1, 2004; 66(6): 1361 - 1371. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Asakura, H. Uchida, H. Miyachi, H. Kobayashi, Y. Miyakawa, S. D. Nimer, H. Takahashi, Y. Ikeda, and M. Kizaki TEL/AML1 Overcomes Drug Resistance Through Transcriptional Repression of Multidrug Resistance-1 Gene Expression Mol. Cancer Res., June 1, 2004; 2(6): 339 - 347. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-Q. Liu, M. F. Morton, A. Reik, R. de la Rosa, M. C. Mendel, X.-Y. Li, C. C. Case, C. O. Pabo, V. Moreno, A. Kempf, et al. Cell Lines for Drug Discovery: Elevating Target-Protein Levels Using Engineered Transcription Factors J Biomol Screen, February 1, 2004; 9(1): 44 - 51. [Abstract] [PDF]
|
|
|
|
|
|
T. G. Uil, H. J. Haisma, and M. G. Rots Therapeutic modulation of endogenous gene function by agents with designed DNA-sequence specificities Nucleic Acids Res., November 1, 2003; 31(21): 6064 - 6078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. V. Bartsevich, J. C. Miller, C. C. Case, and C. O. Pabo Engineered Zinc Finger Proteins for Controlling Stem Cell Fate Stem Cells, November 1, 2003; 21(6): 632 - 637. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tan, D. Guschin, A. Davalos, Y.-L. Lee, A. W. Snowden, Y. Jouvenot, H. S. Zhang, K. Howes, A. R. McNamara, A. Lai, et al. Zinc-finger protein-targeted gene regulation: Genomewide single-gene specificity PNAS, October 14, 2003; 100(21): 11997 - 12002. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Xu, D. Falke, and R. L. Juliano P53-Dependent Cell-Killing by Selective Repression of Thymidine Kinase and Reduced Prodrug Activation Mol. Pharmacol., August 1, 2003; 64(2): 289 - 297. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Falke, M. Fisher, D. Ye, and R. L. Juliano Design of artificial transcription factors to selectively regulate the pro-apoptotic bax gene Nucleic Acids Res., February 1, 2003; 31(3): e10 - e10. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Xu, D. Ye, M. Fisher, and R. L. Juliano Selective Inhibition of P-glycoprotein Expression in Multidrug-Resistant Tumor Cells by a Designed Transcriptional Regulator J. Pharmacol. Exp. Ther., September 1, 2002; 302(3): 963 - 971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ren, T. N. Collingwood, E. J. Rebar, A. P. Wolffe, and H. S. Camp PPARgamma knockdown by engineered transcription factors: exogenous PPARgamma 2 but not PPARgamma 1 reactivates adipogenesis Genes & Dev., January 1, 2002; 16(1): 27 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. W. Scotto and R. A. Johnson Transcription of MDR1: A Therapeutic Target Mol. Interv., June 1, 2001; 1(2): 117 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.L. Juliano, A. Astriab-Fisher, and D. Falke Macromolecular Therapeutics: Emerging Strategies for Drug Discovery in the Postgenome Era Mol. Interv., April 1, 2001; 1(1): 40 - 53. [Abstract] [Full Text]
|
|
|
|
 |
|
 P.-Q. Liu, E. J. Rebar, L. Zhang, Q. Liu, A. C. Jamieson, Y. Liang, H. Qi, P.-X. Li, B. Chen, M. C. Mendel, et al. Regulation of an Endogenous Locus Using a Panel of Designed Zinc Finger Proteins Targeted to Accessible Chromatin Regions. ACTIVATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR A J. Biol. Chem., March 30, 2001; 276(14): 11323 - 11334. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
