| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Genetics, University of Illinois at Chicago, Chicago, Illinois 60612-7309
Genetic suppressor elements (GSEs) are short biologically active gene fragments that encode dominantly acting peptides or inhibitory antisense RNAs. GSEs can be isolated from a single gene or from a multigene complex by constructing a library of short random fragments of the target gene(s) in an expression vector, followed by expression selection for the desired phenotype in a suitable cellular system. GSE selection from a single gene allows one to develop efficient and specific inhibitors of the gene function and to identify functional protein domains. GSE selection from a multigene complex, such as a normalized (uniform abundance) cDNA population from mammalian cells, makes it possible to identify genes that are involved in selectable cellular phenotypes. The potential of GSE selection for uncovering novel gene functions was first demonstrated using bacteriophage 
as a model system. GSE selection in retroviral expression vectors has been applied in mammalian cells to identify genes responsible for sensitivity to etoposide and other chemotherapeutic drugs. GSE selection is also useful for cloning and analysis of tumor suppressor genes and can be applied to identifying tumor-specific targets for future anticancer drugs. Investigators should find this experimental strategy applicable to many different areas of medical and biological research.
1 Based on the Thirteenth C. P. Rhoads Memorial Award Lecture presented at the 85th Annual Meeting of the American Association for Cancer Research, April 12, 1994, San Francisco, CA. This research was supported by National Cancer Institute Grants R37CA40333, R01CA39365, R01CA56736, R01CA62099 (I. B. R.), and R01CA60730 (A. V. G.); postdoctoral fellowship F32CA08851 (C. R. Z.); a grant from Ingenex, Inc.; and a Faculty Research Award from the American Cancer Society, Inc. (I. B. R.).
2 To whom requests for reprints should be addressed, at University of Illinois at Chicago College of Medicine, Department of Genetics (M/C 669), 900 South Ashland Street, Chicago, IL 60607-7170.
3 Present address: Ingenex, Inc., 1505 O'Brien Drive, Menlo Park, CA 94025.
4 Present address: Advanced Cellular Diagnostics, Inc., 925 South Route 83, Elmhurst, IL 60126.
5 Present address: Immunotherapy Division, Baxter Health Care Corp., Route 120 and Wilson Road, Round Lake, IL 60073.
Received 5/ 2/95. Accepted 7/19/95.
This article has been cited by other articles:
|
|
 |
|
  A. P. Komarov, O. W. Rokhlin, C.-A. Yu, and A. V. Gudkov Functional genetic screening reveals the role of mitochondrial cytochrome b as a mediator of FAS-induced apoptosis PNAS, September 23, 2008; 105(38): 14453 - 14458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Machado-Pinilla, I. Sanchez-Perez, J. Ramon Murguia, L. Sastre, and R. Perona A dyskerin motif reactivates telomerase activity in X-linked dyskeratosis congenita and in telomerase-deficient human cells Blood, March 1, 2008; 111(5): 2606 - 2614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Umeda, S. Yano, K. Yamada, and H. Tachibana Green Tea Polyphenol Epigallocatechin-3-gallate Signaling Pathway through 67-kDa Laminin Receptor J. Biol. Chem., February 8, 2008; 283(6): 3050 - 3058. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Gros, C. Delaporte, S. Frey, J. Decesse, B. R. de Saint-Vincent, L. Cavarec, A. Dubart, A. V. Gudkov, and A. Jacquemin-Sablon Identification of New Drug Sensitivity Genes Using Genetic Suppressor Elements: Protein Arginine N-Methyltransferase Mediates Cell Sensitivity to DNA-damaging Agents Cancer Res., January 1, 2003; 63(1): 164 - 171. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. d. l. Alas, G. Los, X. Lin, B. Kurdi-Haidar, G. Manorek, and S. B. Howell Identification of Transdominant-Negative Genetic Suppressor Elements Derived from hMSH2 That Mediate Resistance to 6-Thioguanine Mol. Pharmacol., November 1, 2002; 62(5): 1198 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sanz, L. Mir, and A. Jacquemin-Sablon Bleomycin Resistance in Mammalian Cells Expressing a Genetic Suppressor Element Derived from the SRPK1 Gene Cancer Res., August 1, 2002; 62(15): 4453 - 4458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Carnero, J. D. Hudson, G. J. Hannon, and D. H. Beach Loss-of-function genetics in mammalian cells: the p53 tumor suppressor model Nucleic Acids Res., June 1, 2000; 28(11): 2234 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Lund, M. Duch, and F. S. Pedersen Selection of functional tRNA primers and primer binding site sequences from a retroviral combinatorial library: identification of new functional tRNA primers in murine leukemia virus replication Nucleic Acids Res., February 1, 2000; 28(3): 791 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Gudkov, I. B. Roninson, R. Brown;, A. Kimchi, O. Cohen, J. Kissil, T. Raveh, B. Inbal, N. Levy-Strumpf, H. Berissi, et al. Functional Approaches to Gene Isolation in Mammalian Cells Science, July 16, 1999; 285(5426): 299a - 299. [Full Text]
|
|
|
|
|
|
T. Raveh, H. Berissi, M. Eisenstein, T. Spivak, and A. Kimchi A functional genetic screen identifies regions at the C-terminal tail and death-domain of death-associated protein kinase that are critical for its proapoptotic activity PNAS, February 15, 2000; 97(4): 1572 - 1577. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Cancer Research | Clinical Cancer Research |
| Cancer Epidemiology Biomarkers & Prevention | Molecular Cancer Therapeutics |
| Molecular Cancer Research | Cancer Prevention Research |
| Cancer Prevention Journals Portal | Cancer Reviews Online |
| Annual Meeting Education Book | Meeting Abstracts Online |
