Chemistry: molecular biology and microbiology – Vector – per se
Patent
1996-07-31
1999-08-24
Railey, II, Johnny F.
Chemistry: molecular biology and microbiology
Vector, per se
536 234, 536 235, C12N 1511, C12N 1512, C12N 1562, C12N 1563
Patent
active
059424338
ABSTRACT:
Acidic amino acid extensions to multimeric nucleic acid (e.g., DNA or RNA) binding proteins provide novel nucleic acid binding proteins which can inhibit the function of cellular proteins, thereby regulating and controlling cell growth. The nucleic acid binding proteins are engineered to contain a plurality of acidic amino acids appended to the proteins, generally as extensions of the multimerization or dimerization domain at the amino terminus. The acidically extended nucleic acid binding proteins act as potent dominant negatives which were demonstrated to inhibit the activation of endogenous transactivators, such as AP1. The invention provides novel methods to create DNA binding proteins which can specifically and stably heterodimerize with cellular regulatory proteins and control cell growth. Suitable nucleic acid binding proteins for acidic extensions include members of transcription regulatory protein families, e.g., bZIP and HLH proteins, having characteristic leucine zipper motifs and helix-loop-helix motifs, respectively. The amino terminal extensions of the basic regions of nucleic acid binding proteins are comprised of a sequence of amino acid residues, all or some of which are acidic in nature, and produce robust dominant negatives to the native counterpart proteins in the cell. The acidic amino terminal extension affords a unique protein-protein interaction surface and allows stable multimerization or dimerization between a native protein and the acidically extended protein, thereby controlling, via inhibition or inactivation, the functions of cellular protein products of diverse species, including plants, animals, microorganisms, and viruses.
REFERENCES:
patent: 5545563 (1996-08-01), Darlington et al.
Gonzalez et al., Nature 337:749-752 (1989).
van Straaten et al., Proc. Natl. Acad. Sci. USA 80:3183-3187 (1983).
Izawa, Biochemica et Biophysica Acta 1216:492-494 (1993).
Nature Biotechnology 15:815 (1997).
Verma et al., Nature 389:239-242 (1997).
"Report and Recommendations of the Panel to Assess the NIH Investment in Research on Gene Therapy," Orkin and Motulsky, Co-chairs, Dec. 7, 1995.
B. Amati et al., 1992, "Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max", Nature, 359:423-426.
AD Baxevanis et al., 1993, "Interactions of coiled coils in transcription factors: where is the specificity?", Current Opinions in Genetics and Development, 3:278-285.
PH Brown et al., 1994, "Mechanism of action of a dominant-negative mutant of c-Jun", Oncogene, 9:791-799.
EK O'Shea et al., 1991, "X-ray Structure of the GCN4 Leucine Zipper, a Two-Stranded, Parallel Coiled Coil", Science, 254:539-544.
EK O'Shea et al., 1989, "Evidence that the Leucine Zipper is a Coiled Coil", Science, 243:538-542.
EK O'Shea et al., 1989, "Preferential Heterodimer Formation by Isolated Leucine Zippers from Fos and Jun", Science, 245:646-648.
TG Oas et al, 1990, "Secondary Structure of a Leucine Zipper Determined by Nuclear Magnetic Resonance Spectroscopy", Biochemistry, 29:2891-2894.
JC Hu et al., 1990, "Sequence Requirements for Coiled-Coils: Analysis with .lambda. Repressor-GCN4 Leucine Zipper Fusions", Science, 250:1400-1403.
AD Frankel et al., 1991, "Modular Structure of Transcription Factors: Implications for Gene Regulation", Cell, 65:717-719.
EK O'Shea et al., 1992, "Mechanism of Specificity in the Fos-Jun Oncoprotein Heterodimer", Cell, 68:699-708.
K. Kataoka et al., 1995, "Small Maf Proteins Heterodimerize with Fos and May Act as Competitive Repressors of the NF-E2 Transcription Factor", Molecular and Cellular Biology, 15:2180-2190.
C. Muhle-Goll et al., 1994, "The Dimerization Stability of the HLH-LZ Transcription Protein Family is Modulated by the Leucine Zippers: A CD and NMR Study of TFEB and c-Myc", Biochemistry, 33:11296-11306.
M. Billaud et al., 1993, "A dominant-negative mutant of Max that inhibits sequence-specific DNA binding by Myc proteins", Proc. Natl. Acad. Sci. USA, 90:2739-2743.
Krylov Dmitry
Vinson Charles R.
Railey II Johnny F.
The United States of America as represented by the Department of
LandOfFree
Extension of a protein-protein interaction surface to inactivate does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Extension of a protein-protein interaction surface to inactivate, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Extension of a protein-protein interaction surface to inactivate will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-466807