Targeted polypeptide degradation

Church, George M; Janse, Daniel M

Title: Targeted polypeptide degradation

Patent · Tue May 13 00:00:00 EDT 2008

OSTI ID:983006

Church, George M ^[1]; Janse, Daniel M ^[1]

Brookline, MA

This invention pertains to compositions, methods, cells and organisms useful for selectively localizing polypeptides to the proteasome for degradation. Therapeutic methods and pharmaceutical compositions for treating disorders associated with the expression and/or activity of a polypeptide by targeting these polypeptides for degradation, as well as methods for targeting therapeutic polypeptides for degradation and/or activating therapeutic polypeptides by degradation are provided. The invention provides methods for identifying compounds that mediate proteasome localization and/or polypeptide degradation. The invention also provides research tools for the study of protein function.

View Patent

Cite

Export

Save

Research Organization:: Harvard University

Sponsoring Organization:: USDOE

DOE Contract Number:: FG02-87ER60565

Assignee:: President and Fellows of Harvard College (Cambridge, MA)

Patent Number(s):: 7,371,539

Application Number:: 11/003,103

OSTI ID:: 983006

Country of Publication:: United States

Language:: English

References (65)

The Ubiquitin System Hershko, Avram; Ciechanover, Aaron Annual Review of Biochemistry, Vol. 67, Issue 1 https://doi.org/10.1146/annurev.biochem.67.1.425	journal	June 1998
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans Fire, Andrew; Xu, SiQun; Montgomery, Mary K. Nature, Vol. 391, Issue 6669 https://doi.org/10.1038/35888	journal	February 1998
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality Li, En; Bestor, Timothy H.; Jaenisch, Rudolf Cell, Vol. 69, Issue 6 https://doi.org/10.1016/0092-8674(92)90611-F	journal	June 1992
Construction of a set of convenientsaccharomyces cerevisiae strains that are isogenic to S288C Winston, Fred; Dollard, Catherine; Ricupero-Hovasse, Stephanie L. Yeast, Vol. 11, Issue 1 https://doi.org/10.1002/yea.320110107	journal	January 1995
Forced engagement of a RNA/protein complex by a chemical inducer of dimerization to modulate gene expression Harvey, I.; Garneau, P.; Pelletier, J. Proceedings of the National Academy of Sciences, Vol. 99, Issue 4 https://doi.org/10.1073/pnas.042693399	journal	February 2002
A gated channel into the proteasome core particle Groll, Michael; Bajorek, Monica; Kohler, Alwin Nature Structural Biology https://doi.org/10.2210/pdb1g0u/pdb	journal	November 2000
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. Proceedings of the National Academy of Sciences, Vol. 94, Issue 15 https://doi.org/10.1073/pnas.94.15.7825	journal	July 1997
Development of Protacs to Target Cancer-promoting Proteins for Ubiquitination and Degradation Sakamoto, Kathleen M.; Kim, Kyung B.; Verma, Rati Molecular & Cellular Proteomics, Vol. 2, Issue 12 https://doi.org/10.1074/mcp.T300009-MCP200	journal	October 2003
Applications of Combinatorial Technologies to Drug Discovery. 1. Background and Peptide Combinatorial Libraries Gallop, Mark A.; Barrett, Ronald W.; Dower, William J. Journal of Medicinal Chemistry, Vol. 37, Issue 9 https://doi.org/10.1021/jm00035a001	journal	April 1994
Deadly encounter: ubiquitin meets apoptosis Jesenberger, Veronika; Jentsch, Stefan Nature Reviews Molecular Cell Biology, Vol. 3, Issue 2 https://doi.org/10.1038/nrm731	journal	February 2002
Controlling signal transduction with synthetic ligands Spencer, D.; Wandless, T.; Schreiber, S. Science, Vol. 262, Issue 5136 https://doi.org/10.1126/science.7694365	journal	November 1993
Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation Sakamoto, K. M.; Kim, K. B.; Kumagai, A. Proceedings of the National Academy of Sciences, Vol. 98, Issue 15 https://doi.org/10.1073/pnas.141230798	journal	July 2001
Ca ²⁺ -free Calmodulin and Calmodulin Damaged by in Vitro Aging Are Selectively Degraded by 26 S Proteasomes without Ubiquitination Tarcsa, Edit; Szymanska, Grazyna; Lecker, Stewart Journal of Biological Chemistry, Vol. 275, Issue 27 https://doi.org/10.1074/jbc.M001555200	journal	April 2000
Discovery of Nanomolar Ligands for 7-Transmembrane G-Protein-Coupled Receptors from a Diverse N-(Substituted)glycine Peptoid Library Zuckermann, Ronald N.; Martin, Eric J.; Spellmeyer, David C. Journal of Medicinal Chemistry, Vol. 37, Issue 17 https://doi.org/10.1021/jm00043a007	journal	August 1994
The Axial Channel of the Proteasome Core Particle Is Gated by the Rpt2 ATPase and Controls Both Substrate Entry and Product Release Köhler, Alwin; Cascio, Paolo; Leggett, David S. Molecular Cell, Vol. 7, Issue 6 https://doi.org/10.1016/S1097-2765(01)00274-X	journal	June 2001
Crystal structure of heat shock locus V (HslV) from Escherichia coli Bochtler, M.; Ditzel, L.; Groll, M. Proceedings of the National Academy of Sciences, Vol. 94, Issue 12 https://doi.org/10.1073/pnas.94.12.6070	journal	June 1997
A Novel Procedure for the Synthesis of Libraries Containing Small Organic Molecules Carell, Thomas; Wintner, Edward A.; Bashir-Hashemi, A. Angewandte Chemie International Edition in English, Vol. 33, Issue 20 https://doi.org/10.1002/anie.199420591	journal	November 1994
Structural determinants for the binding of ubiquitin-like domains to the proteasome Mueller, T. D. The EMBO Journal, Vol. 22, Issue 18 https://doi.org/10.1093/emboj/cdg467	journal	September 2003
Ubiquitinylation is not an absolute requirement for degradation of c- Jun protein by the 26 S proteasome Jariel-Encontre, I.; Pariat, M.; Martin, F. Journal of Biological Chemistry, Vol. 270, Issue 19 https://doi.org/10.1074/jbc.270.19.11623	journal	May 1995
Viable offspring derived from fetal and adult mammalian cells Wilmut, I.; Schnieke, A. E.; McWhir, J. Nature, Vol. 385, Issue 6619 https://doi.org/10.1038/385810a0	journal	February 1997
Recombinase-mediated gene activation and site-specific integration in mammalian cells O'Gorman, S.; Fox, D.; Wahl, G. Science, Vol. 251, Issue 4999 https://doi.org/10.1126/science.1900642	journal	March 1991
The Proteasome Bochtler, Matthias; Ditzel, Lars; Groll, Michael Annual Review of Biophysics and Biomolecular Structure, Vol. 28, Issue 1 https://doi.org/10.1146/annurev.biophys.28.1.295	journal	June 1999
Modifying the mammalian genome by gene targeting Bradley, A. Current Opinion in Biotechnology, Vol. 2, Issue 6 https://doi.org/10.1016/S0958-1669(05)80114-4	journal	December 1991
A humanized system for pharmacologic control of gene expression Rivera, Victor M.; Clackson, Tim; Natesan, Sridaran Nature Medicine, Vol. 2, Issue 9 https://doi.org/10.1038/nm0996-1028	journal	September 1996
ATP-Dependent Proteases Degrade Their Substrates by Processively Unraveling Them from the Degradation Signal Lee, Cheolju; Schwartz, Michael P.; Prakash, Sumit Molecular Cell, Vol. 7, Issue 3 https://doi.org/10.1016/S1097-2765(01)00209-X	journal	March 2001
HeterologousHIS3 Marker and GFP Reporter Modules for PCR-Targeting inSaccharomyces cerevisiae Wach, Achim; Brachat, Arndt; Alberti-Segui, Christina Yeast, Vol. 13, Issue 11, p. 1065-1075 https://doi.org/10.1002/(SICI)1097-0061(19970915)13:11<1065::AID-YEA159>3.0.CO;2-K	journal	September 1997
Activation of the Raf-1 kinase cascade by coumermycin-induced dimerization Farrar, Michael A.; Alberola-lla, José; Perlmutter, Roger M. Nature, Vol. 383, Issue 6596 https://doi.org/10.1038/383178a0	journal	September 1996
An Unnatural Biopolymer Cho, Charles Y.; Moran, Edmund J.; Cherry, Sara R. Science, Vol. 261, Issue 5126, p. 1303-1305 https://doi.org/10.1126/science.7689747	journal	September 1993
Searching for peptide ligands with an epitope library Scott, J.; Smith, G. Science, Vol. 249, Issue 4967 https://doi.org/10.1126/science.1696028	journal	July 1990
In vivo half-life of a protein is a function of its amino-terminal residue Bachmair, A.; Finley, D.; Varshavsky, A. Science, Vol. 234, Issue 4773 https://doi.org/10.1126/science.3018930	journal	October 1986
Dexamethasone−Methotrexate: An Efficient Chemical Inducer of Protein Dimerization In Vivo Lin, Hening; Abida, Wassim M.; Sauer, Robert T. Journal of the American Chemical Society, Vol. 122, Issue 17 https://doi.org/10.1021/ja9941532	journal	May 2000
"Diversomers": an approach to nonpeptide, nonoligomeric chemical diversity. DeWitt, S. H.; Kiely, J. S.; Stankovic, C. J. Proceedings of the National Academy of Sciences, Vol. 90, Issue 15 https://doi.org/10.1073/pnas.90.15.6909	journal	August 1993
A Solution-Phase Screening Procedure for the Isolation of Active Compounds from a Library of Molecules Carell, Thomas; Wintner, Edward A.; Rebek, Julius Angewandte Chemie International Edition in English, Vol. 33, Issue 20 https://doi.org/10.1002/anie.199420611	journal	November 1994
Targeted modification and transportation of cellular proteins Colas, P.; Cohen, B.; Ferrigno, P. K. Proceedings of the National Academy of Sciences, Vol. 97, Issue 25 https://doi.org/10.1073/pnas.97.25.13720	journal	December 2000
Screening for receptor ligands using large libraries of peptides linked to the C terminus of the lac repressor. Cull, M. G.; Miller, J. F.; Schatz, P. J. Proceedings of the National Academy of Sciences, Vol. 89, Issue 5 https://doi.org/10.1073/pnas.89.5.1865	journal	March 1992
Substrate access and processing by the 20S proteasome core particle Groll, Michael; Huber, Robert The International Journal of Biochemistry & Cell Biology, Vol. 35, Issue 5 https://doi.org/10.1016/S1357-2725(02)00390-4	journal	May 2003
α-Synuclein metabolism and aggregation is linked to ubiquitin-independent degradation by the proteasome Tofaris, George K.; Layfield, Robert; Spillantini, Maria Grazia FEBS Letters, Vol. 509, Issue 1 https://doi.org/10.1016/S0014-5793(01)03115-5	journal	November 2001
A proteasomal ATPase subunit recognizes the polyubiquitin degradation signal Lam, Y. Amy; Lawson, T. Glen; Velayutham, Murugesan Nature, Vol. 416, Issue 6882 https://doi.org/10.1038/416763a	journal	April 2002
Tet repressor-based system for regulated gene expression in eukaryotic cells: Principles and advances Baron, Udo; Bujard, Hermann Methods in Enzymology https://doi.org/10.1016/S0076-6879(00)27292-3	book	January 2000
The structures of HslU and the ATP-dependent protease HslU–HslV Bochtler, Matthias; Hartmann, Claudia; Song, Hyun Kyu Nature, Vol. 403, Issue 6771 https://doi.org/10.1038/35001629	journal	February 2000
Recognition of Misfolding Proteins by PA700, the Regulatory Subcomplex of the 26 S Proteasome Strickland, Elizabeth; Hakala, Kevin; Thomas, Philip J. Journal of Biological Chemistry, Vol. 275, Issue 8 https://doi.org/10.1074/jbc.275.8.5565	journal	February 2000
A new efficient gene disruption cassette for repeated use in budding yeast Guldener, U. Nucleic Acids Research, Vol. 24, Issue 13 https://doi.org/10.1093/nar/24.13.2519	journal	July 1996
Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast Heitman, J.; Movva, N.; Hall, M. Science, Vol. 253, Issue 5022 https://doi.org/10.1126/science.1715094	journal	August 1991
Selection of antibody ligands from a large library of oligopeptides expressed on a multivalent exposition vector Felici, Franco; Castagnoli, Luisa; Musacchio, Andrea Journal of Molecular Biology, Vol. 222, Issue 2 https://doi.org/10.1016/0022-2836(91)90213-P	journal	November 1991
PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone Benaroudj, Nadia; Goldberg, Alfred L. Nature Cell Biology, Vol. 2, Issue 11 https://doi.org/10.1038/35041081	journal	October 2000
Regulation of cellular polyamines by antizyme Coffino, Philip Nature Reviews Molecular Cell Biology, Vol. 2, Issue 3 https://doi.org/10.1038/35056508	journal	March 2001
Peptides on phage: a vast library of peptides for identifying ligands Cwirla, S. E.; Peters, E. A.; Barrett, R. W. Proceedings of the National Academy of Sciences, Vol. 87, Issue 16, p. 6378-6382 https://doi.org/10.1073/pnas.87.16.6378	journal	August 1990
TOR Mutations Confer Rapamycin Resistance by Preventing Interaction with FKBP12-Rapamycin Lorenz, Michael C.; Heitman, Joseph Journal of Biological Chemistry, Vol. 270, Issue 46 https://doi.org/10.1074/jbc.270.46.27531	journal	November 1995
Structure of 20S proteasome from yeast at 2.4Å resolution Groll, Michael; Ditzel, Lars; Löwe, Jan Nature, Vol. 386, Issue 6624 https://doi.org/10.1038/386463a0	journal	April 1997
The Sizes of Peptides Generated from Protein by Mammalian 26 and 20 S Proteasomes: IMPLICATIONS FOR UNDERSTANDING THE DEGRADATIVE MECHANISM AND ANTIGEN PRESENTATION Kisselev, Alexei F.; Akopian, Tatos N.; Woo, Kee Min Journal of Biological Chemistry, Vol. 274, Issue 6 https://doi.org/10.1074/jbc.274.6.3363	journal	February 1999
Controlling protein association and subcellular localization with a synthetic ligand that induces heterodimerization of proteins. Belshaw, P. J.; Ho, S. N.; Crabtree, G. R. Proceedings of the National Academy of Sciences, Vol. 93, Issue 10 https://doi.org/10.1073/pnas.93.10.4604	journal	May 1996
Chemically induced dimerization of dihydrofolate reductase by a homobifunctional dimer of methotrexate Kopytek, Stephan J.; Standaert, Robert F.; Dyer, John CD Chemistry & Biology, Vol. 7, Issue 5 https://doi.org/10.1016/S1074-5521(00)00109-5	journal	May 2000
Structural basis for the activation of 20S proteasomes by 11S regulators Whitby, Frank G.; Masters, Eugene I.; Kramer, Larissa Nature, Vol. 408, Issue 6808 https://doi.org/10.1038/35040607	journal	November 2000
Recursive deconvolution of combinatorial chemical libraries. Erb, E.; Janda, K. D.; Brenner, S. Proceedings of the National Academy of Sciences, Vol. 91, Issue 24 https://doi.org/10.1073/pnas.91.24.11422	journal	November 1994
Protein unfolding — an important process in vivo? Matouschek, Andreas Current Opinion in Structural Biology, Vol. 13, Issue 1 https://doi.org/10.1016/S0959-440X(03)00010-1	journal	February 2003
Multiplexed biochemical assays with biological chips Fodor, Stephen P. A.; Rava, Richard P.; Huang, Xiaohua C. Nature, Vol. 364, Issue 6437 https://doi.org/10.1038/364555a0	journal	August 1993
Targeted oncogene activation by site-specific recombination in transgenic mice. Lakso, M.; Sauer, B.; Mosinger, B. Proceedings of the National Academy of Sciences, Vol. 89, Issue 14 https://doi.org/10.1073/pnas.89.14.6232	journal	July 1992
Site-directed mutagenesis by gene targeting in mouse embryo-derived stem cells Thomas, Kirk R.; Capecchi, Mario R. Cell, Vol. 51, Issue 3 https://doi.org/10.1016/0092-8674(87)90646-5	journal	November 1987
Random peptide libraries: a source of specific protein binding molecules Devlin, J.; Panganiban, L.; Devlin, P. Science, Vol. 249, Issue 4967 https://doi.org/10.1126/science.2143033	journal	July 1990
Dimeric ligands define a role for transcriptional activation domains in reinitiation Ho, Steffan N.; Biggar, Stephen R.; Spencer, David M. Nature, Vol. 382, Issue 6594 https://doi.org/10.1038/382822a0	journal	August 1996
A new type of synthetic peptide library for identifying ligand-binding activity Lam, Kit S.; Salmon, Sydney E.; Hersh, Evan M. Nature, Vol. 354, Issue 6348 https://doi.org/10.1038/354082a0	journal	November 1991
Role of the proteasome and NF- B in streptococcal cell wall-induced polyarthritis Palombella, V. J.; Conner, E. M.; Fuseler, J. W. Proceedings of the National Academy of Sciences, Vol. 95, Issue 26 https://doi.org/10.1073/pnas.95.26.15671	journal	December 1998
Determinants of proteasome recognition of ornithine decarboxylase, a ubiquitin-independent substrate Zhang, M. The EMBO Journal, Vol. 22, Issue 7 https://doi.org/10.1093/emboj/cdg158	journal	April 2003
Proteasomal degradation of tau protein: Tau and the proteasome David, Della C.; Layfield, Robert; Serpell, Louise Journal of Neurochemistry, Vol. 83, Issue 1 https://doi.org/10.1046/j.1471-4159.2002.01137.x	journal	September 2002
The base of the proteasome regulatory particle exhibits chaperone-like activity Braun, Beate C.; Glickman, Michael; Kraft, Regine Nature Cell Biology, Vol. 1, Issue 4 https://doi.org/10.1038/12043	journal	July 1999

Similar Records

The induction of heme oxygenase-1 suppresses heat shock protein 90 and the proliferation of human breast cancer cells through its byproduct carbon monoxide

Journal Article · Wed Jan 01 00:00:00 EST 2014 · Toxicology and Applied Pharmacology · OSTI ID:983006

Lee, Wen-Ying; Chen, Yen-Chou; Shih, Chwen-Ming; +4 more

Endothelial monocyte activating polypeptide-II modulates endothelial cell responses by degrading hypoxia-inducible factor-1alpha through interaction with PSMA7, a component of the proteasome

Journal Article · Wed Jul 01 00:00:00 EDT 2009 · Experimental Cell Research · OSTI ID:983006

Tandle, Anita T.; Calvani, Maura; Uranchimeg, Badarch; +2 more

SIRT1 inhibits proliferation of pancreatic cancer cells expressing pancreatic adenocarcinoma up-regulated factor (PAUF), a novel oncogene, by suppression of {beta}-catenin

Journal Article · Fri Jun 29 00:00:00 EDT 2012 · Biochemical and Biophysical Research Communications · OSTI ID:983006

Cho, Il-Rae; Koh, Sang Seok; Malilas, Waraporn; +6 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Title: Targeted polypeptide degradation

Citation Formats

References (65)

Similar Records

Related Subjects