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(12) United States Patent (10) Patent No.: US 8,361,780 B2 Gaertig Et Al USOO836.1780B2 (12) United States Patent (10) Patent No.: US 8,361,780 B2 Gaertig et al. (45) Date of Patent: Jan. 29, 2013 (54) BIOLOGICAL SYSTEMAND ASSAY FOR Adoutte et al., “Microtubule diversity in ciliated cells: evidence for its IDENTIFYING MODULATORS OF TUBULIN generation by post-translational modification in the axonemes of LGASES Paramecium and quail oviduct cells.” 1991 Biol. Cell 71:227-245. Alexander et al., "Characterization of posttranslational modifications in neuron-specific class III beta-tubulin by mass spectrometry.” Jun. (75) Inventors: Jacek Gaertig, Athens, GA (US); 1, 1991 Proc. Natl. Acad. Sci. USA 88:4685-4689. Dorota Wloga, Legionowo (PL); Swati Artymiuket al., “Biotin carboxylase comes into the fold.” Feb. 1996 M. Suryavanshi, Pittsburgh, PA (US) Nat. Struct. Biol. 3:128-132. Attwell et al., “A temperature-sensitive mutation affecting synthesis (73) Assignee: University of Georgia Research of outer arm dyneins in Tetrahymena thermophila.” Mar.-Apr. 1992.J. Foundation, Inc., Athens, GA (US) Protozool. 39,261-266. Audebert et al., “Reversible Polyglutamylation of O- and B-Tubulin (*) Notice: Subject to any disclaimer, the term of this and Microtubule Dynamics in Mouse Brain Neurons.” Jun. 1993 patent is extended or adjusted under 35 Mol. Biol. Cell 4:615-626. U.S.C. 154(b) by 241 days. Audebert et al., “Developmental regulation of polyglutamylated alpha- and beta-tubulin in mouse brain neurons.” Aug. 1994.J. Cell (21) Appl. No.: 12/6S8,487 Sci. 107(Pt. 8): 2313-2322. Backofen et al., “Cloning and characterization of the mammalian (22) Filed: Feb. 5, 2010 specific nicolin 1 gene (NICNI) encoding a nuclear 24 kDa protein.” Nov. 2002 Eur: J. Biochem. 269(21):5240-5245. (65) Prior Publication Data Bacon et al., “A Fast Algorithm for Rendering Space-Filling Mol ecule Pictures.” 1988.J. Mol. Graph. 6:219-220. US 2010/0261220 A1 Oct. 14, 2010 Bagdasarian and Bagdasarian, "Chapter 18: Gene Cloning and Expression.” in Methods for General and Molecular Bacteriology, Related U.S. Application Data Gerhardt et al. (eds.). American Society for Microbiology: Washing ton, D.C.; 1994. Title page, publisher's page, and pp. 406-417. (63) Continuation-in-part of application No. 1 1/479,098, Barlow et al., “Paclitaxel-dependent mutants have severely reduced filed on Jun. 30, 2006, now abandoned. microtubule assembly and reduced tubulin synthesis.” Sep. 1, 2002.J. Cell Sci. 115:3469-3478. (60) Provisional application No. 60/695,776, filed on Jun. Bhattacharyya et al., "Tubulin, hybrid dimers, and tubulin S. 30, 2005. Stepwise charge reduction and polymerization.” Aug. 25, 1985 J. Biol. Chen. 260:10208-10216. (51) Int. Cl. Bobinnec et al., “Glutamylation of Centriole and Cytoplasmic CI2N L/10 (2006.01) Tubulin in Proliferating Non-neuronal Cells.” 1998 Cell Motil. CI2N 15/74 (2006.01) Cytoskeleton 39:223-232. CI2O I/02 (2006.01) Bobinnec et al., “Centriole Disassembly in vivo and Its Effect on Centrosome Structure and Function in Vertebrate Cells.” Dec. 1998.J. CI2P I/O (2006.01) Cell Biol. 143(6): 1575-1589. (52) U.S. Cl. .......... 435/258.1; 435/29: 435/471; 435/41 Bonnetet al., “Differential Binding Regulation of Microtubule-asso (58) Field of Classification Search ............... 435/258.1, ciated Proteins MAP1A, MAP1B, and MAP2 by Tubulin 435/29, 471, 41 Polyglutamylation.” Apr. 2001 J. Biol. Chem. 276(16): 12839-12848. See application file for complete search history. Boucher et al., “Polyglutamylation of Tubulinas a Progressive Regu lator of in Vitro Interactions between the Microtubule-associated (56) References Cited Protein Tau and Tubulin.” 1994, Biochemistry, Oct. 33(41): 12471 12477. Bradbury et al., “Histone deacetylases in acute myeloid leukaemia U.S. PATENT DOCUMENTS show a distinctive pattern of expression that changes selectively in 6,846,481 B1 1/2005 Gaertig et al. response to deacetylase inhibitors.” Oct. 2005 Leukemia 2003/0027192 A1 2/2003 Gorovsky et al. 19(10): 1751-1759. 2005/0106164 A1 5/2005 Gaertig et al. Bré et al., “Glutamylated Tubulin Probed in Ciliates With the 2007/0031927 A1 2/2007 Gaertig et al. Monoclonal Antibody GT335.” 1994 Cell Motility and the FOREIGN PATENT DOCUMENTS Cytoskeleton 27(4):337-349. Bré et al., “Axonemal tubulin polyglycylation probed with two WO WOOOf 46.381 A1 8, 2000 monoclonal antibodies: widespread evolutionary distribution, OTHER PUBLICATIONS appearance during spermatozoan maturation and possible function in motility.” Apr. 1996.J. Cell Sci. 109:727-738. Janke et al., Tubulin polyglutamylase enzymes are members of the TTL domain protein family. Science, vol. 308: 1758-1762.* (Continued) Wloga et al., Glutamylation on a-tubulin is not essential but affects the assembly and functions of a Subset of microtubules in Primary Examiner — Ganapathirama Raghu Tetrahymena thermophila Eukaryotic Cell, 2008, vol. 7 (8): 1362 (74) Attorney, Agent, or Firm — Mueting Raasch & 1372.* Gebhardt, PA. Wloga et al., TTLL3 is tubulin glycine ligase that regulates the assembly of cilia. Developmental Cell, 2009, vol. 16: 867-876.* (57) ABSTRACT Wloga et al., Hyperglutamylation of tubulin can either stabilize or destabilize microtubules in the same cell. Eukaryotic Cell, 2010, Vo. Tetrahymena is used as a host cell in a biological assay for 9 (1): 184-193.* identification of modulators of tubulin ligases. Abal et al., “Centrioles resist forces applied on centrosomes during G2/M transition. Jun. 2005 Biol. Cell 97:425-434. 16 Claims, 44 Drawing Sheets US 8,361.780 B2 Page 2 OTHER PUBLICATIONS Duan and Gorovsky, “Both carboxy-terminal tails of alpha- and beta-tubulin are essential, but either one will suffice.” Feb. 19, 2002 Bré et al., "Tubulin polyglycylation: differential posttranslational Curr: Biol. 12:313-316. modification of dynamic cytoplasmic and stable axonemal Dupuis, "The beta-tubulin genes of Paramecium are interrupted by microtubules in paramecium.” Sep. 1998 Mol. Biol. Cell 9:2655 two 27 by introns.” Oct. 1992 EMBO.J. 11:37 13-3719. 2665. Dupuis-Williams et al., “The tubulin gene family of Paramecium: Bressac et al., "A massive new posttranslational modification occurs characterization and expression of the alpha PT1 and alpha PT2 on axonemal tubulin at the final step of speimatogenesis in genes which code for alpha-tubulins with unusual C-terminal amino Drosophila,” Aug. 1995 Eur: J Cell Biol. 67:346-355. acids, GLY and ALA' 1996 Biol. Cell 87:83-93. Brooks et al., "CHARMM: A Program for Macromolecular Energy, Dymek et al., "PF15p is the Chlamydomonas homologue of the Minimization, and Dynamic Calculations.” 1983 J Comp. Chem. Katanin p80 subunit and is required for assembly of flagellar central 4(2): 187-217. microtubules.” Aug. 2004 Eukaryot. Cell 3:870-879. Brown et al., "Hypoxia Regulates Assembly of Cilia in Suppressors Edde et al., “Posttranslational Glutamylation of O-Tubulin.” Jan. of Tetrahymena Lacking an Intraflagellar Transport Subunit Gene.” 1990 Science 247(4938):83-85. Aug. 2003 Mol. Biol. Cell 14:3192-3207. Available online May 3, Eisen, et al., “Macronuclear Genome Sequence of the Ciliate 2003. Tetrahymena thermophila, a Model Eukaryote.” Online publication Bucher et al., "A Flexible Motif Search Technique Based on Gener Aug. 29, 2006; DOI: 10.1371/journalpbio.0040286. Retrieved on alized Profiles.” 1996 Comput Chem. 20(1):3-23. Dec. 13, 2006). Retrieved from the Internet: <URL:biology. Burdine and Schier, "Conserved and divergent mechanisms in left plosjournals.org/perlserv/?request get-document&doi=10.1371/ right axis formation.” Apr. 1, 2000 Genes Dev. 14:763-776. joumalpbio,0040286>; 77 pages. Bylund, et al., “Replication Protein A-Directed Unloading of PCNA Eisen et al., “Macronuclear Genome Sequence of the Ciliate by the Ctf18 Cohesion Establishment Complex,” Jul. 2005 Mol. Biol. Tetrahymena thermophila, a Model Eukaryote.” Sep. 2006. PloS Cell 25(13):5445-5455. Biol. 4(9)(e286): 1620-1642. Callen et al., “Isolation and characterization of libraries of Eisenstadt et al., "Chapter 13: Gene Mutation.” in Methods for Gen monoclonal antibodies directed against various forms of tubulin in eral and Molecular Bacteriology, Gerhardt et al. (eds.). American Paramecium.” 1994 Biol. Cell 81:95-119. Society for Microbiology: Washington, D.C.; 1994. Title page, pub Campbell et al., “Mutation of a Novel Gene Results in Abnormal lisher's page, and pp. 297-316. Development of Spermatid Flagella, Loss of Intermale Aggression Ersfeld et al., "Characterization of the Tubulin-Tyrosine Ligase.” and Reduced Body Fat in Mice.” Sep. 2002 Genetics 162:307-320. Feb. 1993.J. Cell Biol. 120(3):725-732. Carter et al., "Structure and functional role of dynein's microtubule Essner et al., "Kupffer's vesicle is a ciliated organ of asymmetry in binding domain.” Dec. 12, 2008 Science 322:1691-1695. the Zebrafish embryo that initiates left-right development of the brain, Cassidy-Hanley et al., "Germline and Somatic Transformation of heart and gut.” Mar. 2005 Development 132:1247-1260. Available Mating Tetrahymena thermophila by Particle Bombardment.” May online Feb. 16, 2005. 1997 Genetics 146:135-147. Fahmy, "Study identifies critical traffic engineer of the nervous Cheung et al., "A small-molecule inhibitor of skeletal muscle myosin system.” Franklin News Sep. 8, 2010. Available online retrieved on II.” Jan. 2002 Nat. Cell. Biol. 4:83-88. Available online Dec. 17, Jun. 26, 2012). Retrieved from the Internet: <http://www.franklin. 2001. uga.edu/news/articles/1000/traffic engineer.html>; 2 pages. Cheung et al., “AIDS-Related Malignancies: Emerging Challenges in Felsenstein, "An Alternating Least Squares Approach to Inferring the Era of Highly Active Antiretroviral Therapy.” Jun.-Jul. 2005 The Phylogenies from Pairwise Distances.” Mar. 1997 Systematic Biol Oncologist, Lymphoma 10:412-426. ogy 46(1): 101-111. Chilcoat, et al., “Granule Lattice Protein 1 (Grillp), an Acidic, Cal Fennell et al., “Isotype expression, post-translational modification cium-Binding Protein in Tetrahymena thermophila Dense-Core and stage-dependent production of tubulins in erythrocytic Secretory Granules, Influences Granule Size, Shape, Content Orga Plasmodium falciparum.” Apr.
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