Home LiteratureArticle Details
PMID: 10637228 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

D-TACC: a novel centrosomal protein required for normal spindle function in the early Drosophila embryo.

The EMBO journal ·Vol. 19 ·No. 2 ·2000-01-17 ·Pages 241-52

Gergely F, Kidd D, Jeffers K, Wakefield JG, Raff JW

Abstract

We identify Drosophila TACC (D-TACC) as a novel protein that is concentrated at centrosomes and interacts with microtubules. We show that D-TACC is essential for normal spindle function in the early embryo; if D-TACC function is perturbed by mutation or antibody injection, the microtubules emanating from centrosomes in embryos are short and chromosomes often fail to segregate properly. The C-terminal region of D-TACC interacts, possibly indirectly, with microtubules, and can target a heterologous fusion protein to centrosomes and microtubules in embryos. This C-terminal region is related to the mammalian transforming, acidic, coiled-coil-containing (TACC) family of proteins. The function of the TACC proteins is unknown, but the genes encoding the known TACC proteins are all associated with genomic regions that are rearranged in certain cancers. We show that at least one of the mammalian TACC proteins appears to be associated with centrosomes and microtubules in human cells. We propose that this conserved C-terminal 'TACC domain' defines a new family of microtubule-interacting proteins.

MeSH Terms
Amino Acid Sequence Animals Centrosome/physiology Cloning, Molecular Conserved Sequence Drosophila/embryology,genetics Drosophila Proteins Gene Expression Regulation, Developmental Humans Mammals Microtubule-Associated Proteins/chemistry,genetics,metabolism Molecular Sequence Data Protein Structure, Secondary Recombinant Fusion Proteins/metabolism Recombinant Proteins/chemistry,metabolism Sequence Alignment Sequence Homology, Amino Acid Spindle Apparatus/physiology
Chemicals
Drosophila Proteins Microtubule-Associated Proteins Recombinant Fusion Proteins Recombinant Proteins TACC protein, Drosophila
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gergely F
Wellcome/CRC Institute and Department of Genetics, Tennis Court Road, Cambridge CB2 1QR, UK.
Kidd D
Jeffers K
Wakefield J G
Raff J W
References (71)
71 references, click to expand
  1. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
    Gene. 1988 Jul 15;67(1):31-40 PMID: 3047011
  2. GFP in Drosophila.
    Trends Genet. 1995 Aug;11(8):324-5 PMID: 8585131
  3. Microtubule organization and dynamics dependent on microtubule-associated proteins.
    Curr Opin Cell Biol. 1994 Feb;6(1):74-81 PMID: 8167029
  4. Focusing on spindle poles.
    J Cell Sci. 1998 Jun;111 ( Pt 11):1477-81 PMID: 9580556
  5. Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
    Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
  6. A modified method for obtaining large amounts of high titer polyclonal ascites fluid.
    J Immunol Methods. 1993 Sep 27;165(1):75-80 PMID: 8409470
  7. The spindle-assembly checkpoint: aiming for a perfect mitosis, every time.
    Trends Cell Biol. 1996 Jun;6(6):228-34 PMID: 15157461
  8. Identification of a polypeptide associated with the malignant phenotype in acute leukemia.
    J Biol Chem. 1988 Sep 15;263(26):12813-5 PMID: 3417633
  9. Structure and expression of ubiquitin genes of Drosophila melanogaster.
    Mol Cell Biol. 1988 Nov;8(11):4727-35 PMID: 2463465
  10. Two proteins that cycle asynchronously between centrosomes and nuclear structures: Drosophila CP60 and CP190.
    J Cell Sci. 1997 Jul;110 ( Pt 14):1573-83 PMID: 9247191
  11. Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells.
    Proc Natl Acad Sci U S A. 1997 Dec 23;94(26):14506-11 PMID: 9405643
  12. Effects of vinblastine, podophyllotoxin and nocodazole on mitotic spindles. Implications for the role of microtubule dynamics in mitosis.
    J Cell Sci. 1992 Jul;102 ( Pt 3):401-16 PMID: 1506423
  13. Xenopus interphase and mitotic microtubule-associated proteins differentially suppress microtubule dynamics in vitro.
    Cell Motil Cytoskeleton. 1998;41(3):202-13 PMID: 9829775
  14. Centrosomal control of microtubule dynamics.
    Proc Natl Acad Sci U S A. 1999 Jan 5;96(1):115-20 PMID: 9874781
  15. Accessory protein regulation of microtubule dynamics throughout the cell cycle.
    Curr Opin Cell Biol. 1999 Feb;11(1):134-41 PMID: 10047516
  16. Kin I kinesins are microtubule-destabilizing enzymes.
    Cell. 1999 Jan 8;96(1):69-78 PMID: 9989498
  17. The Drosophila gene abnormal spindle encodes a novel microtubule-associated protein that associates with the polar regions of the mitotic spindle.
    J Cell Biol. 1997 May 19;137(4):881-90 PMID: 9151690
  18. The TOGp protein is a new human microtubule-associated protein homologous to the Xenopus XMAP215.
    J Cell Sci. 1998 May;111 ( Pt 10):1371-83 PMID: 9570755
  19. LK6, a short lived protein kinase in Drosophila that can associate with microtubules and centrosomes.
    J Cell Sci. 1997 Jan;110 ( Pt 2):209-19 PMID: 9044051
  20. Abnormal spindle protein, Asp, and the integrity of mitotic centrosomal microtubule organizing centers.
    Science. 1999 Mar 12;283(5408):1733-5 PMID: 10073938
  21. XMAP310: a Xenopus rescue-promoting factor localized to the mitotic spindle.
    J Cell Biol. 1997 Nov 17;139(4):975-83 PMID: 9362515
  22. Effect on microtubule dynamics of XMAP230, a microtubule-associated protein present in Xenopus laevis eggs and dividing cells.
    J Cell Biol. 1994 Dec;127(5):1289-99 PMID: 7962090
  23. Human cyclins A and B1 are differentially located in the cell and undergo cell cycle-dependent nuclear transport.
    J Cell Biol. 1991 Oct;115(1):1-17 PMID: 1717476
  24. Gamma-tubulin is required for the structure and function of the microtubule organizing centre in Drosophila neuroblasts.
    EMBO J. 1995 Jan 3;14(1):28-36 PMID: 7828594
  25. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
    Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4 PMID: 388439
  26. Functional cDNA libraries from Drosophila embryos.
    J Mol Biol. 1988 Sep 20;203(2):425-37 PMID: 3199441
  27. Molecular components of the centrosome.
    Trends Cell Biol. 1993 Apr;3(4):118-28 PMID: 14731766
  28. Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex.
    Nature. 1995 Dec 7;378(6557):578-83 PMID: 8524390
  29. Mutations affecting cell division in Drosophila.
    Methods Cell Biol. 1991;35:543-86 PMID: 1664033
  30. Microtubule polymerization dynamics.
    Annu Rev Cell Dev Biol. 1997;13:83-117 PMID: 9442869
  31. Microtubule dynamics: severing microtubules in mitosis.
    Curr Biol. 1993 Apr 1;3(4):208-10 PMID: 15335768
  32. A microtubule-associated protein from Xenopus eggs that specifically promotes assembly at the plus-end.
    J Cell Biol. 1987 Nov;105(5):2203-15 PMID: 2890645
  33. Balanced regulation of microtubule dynamics during the cell cycle: a contemporary view.
    Bioessays. 1999 Jan;21(1):53-60 PMID: 10070254
  34. Cloning of TACC1, an embryonically expressed, potentially transforming coiled coil containing gene, from the 8p11 breast cancer amplicon.
    Oncogene. 1999 Jul 8;18(27):4032-8 PMID: 10435627
  35. Identification of microtubule-associated proteins in the centrosome, spindle, and kinetochore of the early Drosophila embryo.
    J Cell Biol. 1989 Dec;109(6 Pt 1):2977-91 PMID: 2574177
  36. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  37. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity.
    Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):2950-5 PMID: 9501196
  38. The disappearance of cyclin B at the end of mitosis is regulated spatially in Drosophila cells.
    EMBO J. 1999 Apr 15;18(8):2184-95 PMID: 10205172
  39. Studies of nuclear and cytoplasmic behaviour during the five mitotic cycles that precede gastrulation in Drosophila embryogenesis.
    J Cell Sci. 1983 May;61:31-70 PMID: 6411748
  40. CP60: a microtubule-associated protein that is localized to the centrosome in a cell cycle-specific manner.
    Mol Biol Cell. 1995 Dec;6(12):1673-84 PMID: 8590797
  41. The 190 kDa centrosome-associated protein of Drosophila melanogaster contains four zinc finger motifs and binds to specific sites on polytene chromosomes.
    J Cell Sci. 1995 Nov;108 ( Pt 11):3377-87 PMID: 8586650
  42. Supernumerary centrosomes and cancer: Boveri's hypothesis resurrected.
    Cell Motil Cytoskeleton. 1998;41(4):281-8 PMID: 9858153
  43. Centrosome defects and genetic instability in malignant tumors.
    Cancer Res. 1998 Sep 1;58(17):3974-85 PMID: 9731511
  44. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation.
    Nat Genet. 1998 Oct;20(2):189-93 PMID: 9771714
  45. The third member of the transforming acidic coiled coil-containing gene family, TACC3, maps in 4p16, close to translocation breakpoints in multiple myeloma, and is upregulated in various cancer cell lines.
    Genomics. 1999 Jun 1;58(2):165-70 PMID: 10366448
  46. Mitotic chromatin regulates phosphorylation of Stathmin/Op18.
    Nature. 1997 Oct 9;389(6651):640-3 PMID: 9335509
  47. Distinct roles of PP1 and PP2A-like phosphatases in control of microtubule dynamics during mitosis.
    EMBO J. 1997 Sep 15;16(18):5537-49 PMID: 9312013
  48. Oncoprotein 18 is a phosphorylation-responsive regulator of microtubule dynamics.
    EMBO J. 1996 Oct 1;15(19):5290-8 PMID: 8895574
  49. ZW10 helps recruit dynactin and dynein to the kinetochore.
    J Cell Biol. 1998 Aug 10;142(3):763-74 PMID: 9700164
  50. Microtubule release from the centrosome.
    Proc Natl Acad Sci U S A. 1997 May 13;94(10):5078-83 PMID: 9144193
  51. Purification of a multiprotein complex containing centrosomal proteins from the Drosophila embryo by chromatography with low-affinity polyclonal antibodies.
    Mol Biol Cell. 1992 Jan;3(1):1-11 PMID: 1372522
  52. Characterization of two related Drosophila gamma-tubulin complexes that differ in their ability to nucleate microtubules.
    J Cell Biol. 1999 Feb 22;144(4):721-33 PMID: 10037793
  53. Identification of a protein that interacts with tubulin dimers and increases the catastrophe rate of microtubules.
    Cell. 1996 Feb 23;84(4):623-31 PMID: 8598048
  54. XKCM1: a Xenopus kinesin-related protein that regulates microtubule dynamics during mitotic spindle assembly.
    Cell. 1996 Jan 12;84(1):37-47 PMID: 8548824
  55. The centrosome and cellular organization.
    Annu Rev Biochem. 1994;63:639-74 PMID: 7979251
  56. Dynamic changes in microtubule configuration correlate with nuclear migration in the preblastoderm Drosophila embryo.
    J Cell Biol. 1993 Jul;122(1):113-21 PMID: 8314839
  57. Drosophila gamma-tubulin is part of a complex containing two previously identified centrosomal MAPs.
    J Cell Biol. 1993 May;121(4):823-35 PMID: 8491775
  58. The centrosome--a tiny organelle with big potential.
    Nat Genet. 1998 Oct;20(2):104-6 PMID: 9771694
  59. Fertilization in Drosophila melanogaster: centrosome inheritance and organization of the first mitotic spindle.
    Dev Biol. 1996 Jun 15;176(2):199-208 PMID: 8660861
  60. XMAP from Xenopus eggs promotes rapid plus end assembly of microtubules and rapid microtubule polymer turnover.
    J Cell Biol. 1994 Nov;127(4):985-93 PMID: 7962080
  61. Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells.
    Mol Cell. 1999 Mar;3(3):389-95 PMID: 10198641
  62. Microtubule nucleation by gamma-tubulin-containing rings in the centrosome.
    Nature. 1995 Dec 7;378(6557):638-40 PMID: 8524401
  63. Miranda mediates asymmetric protein and RNA localization in the developing nervous system.
    Genes Dev. 1998 Jun 15;12(12):1847-57 PMID: 9637686
  64. The centrosome.
    Sci Am. 1993 Jun;268(6):62-8 PMID: 8516675
  65. The Drosophila kinesin-like protein KLP3A is required for proper behavior of male and female pronuclei at fertilization.
    Development. 1997 Jun;124(12):2365-76 PMID: 9199363
  66. Morphogenetic properties of microtubules and mitotic spindle assembly.
    Cell. 1996 Feb 9;84(3):401-10 PMID: 8608594
  67. mini spindles: A gene encoding a conserved microtubule-associated protein required for the integrity of the mitotic spindle in Drosophila.
    J Cell Biol. 1999 Sep 6;146(5):1005-18 PMID: 10477755
  68. Live confocal analysis with fluorescently labeled proteins.
    Methods Mol Biol. 1999;122:223-39 PMID: 10231795
  69. Centrosomes, and not nuclei, initiate pole cell formation in Drosophila embryos.
    Cell. 1989 May 19;57(4):611-9 PMID: 2497990
  70. XMAP230 is required for the assembly and organization of acetylated microtubules and spindles in Xenopus oocytes and eggs.
    J Cell Sci. 1998 Aug;111 ( Pt 16):2315-27 PMID: 9683627
  71. Predicting coiled coils from protein sequences.
    Science. 1991 May 24;252(5009):1162-4 PMID: 2031185
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.2.241
Published
2000-01-17
Pages
241-52
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305558
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.2.241 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2