Separate to operate: Control of centrosome positioning and separation

Philosophical Transactions of the Royal Society B: Biological Sciences

Volumn 369, Issue 1650, 2014, Pages

  Agircan, Fikret G ^a   Schiebel, Elmar ^a   Mardin, Balca R ^a,b  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

Author keywords

Centrosome positioning; Centrosome separation; Eg5

Indexed keywords

DYNEIN ADENOSINE TRIPHOSPHATASE; KIF11 PROTEIN, HUMAN; KINESIN; MOLECULAR MOTOR; NEK2 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

CELL CYCLE; CENTRIOLE; CENTROSOME; HUMAN; METABOLISM; MICROTUBULE; PHYSIOLOGY; SPINDLE APPARATUS;

CELL CYCLE; CENTRIOLES; CENTROSOME; DYNEINS; HUMANS; KINESIN; MICROTUBULES; MOLECULAR MOTOR PROTEINS; PROTEIN-SERINE-THREONINE KINASES; SPINDLE APPARATUS;

EID: 84904576048     PISSN: 09628436     EISSN: 14712970     Source Type: Journal    
DOI: 10.1098/rstb.2013.0461     Document Type: Review

References (99)

1. Bettencourt-Dias M, Glover DM. 2007 Centrosome biogenesis and function: centrosomics brings new understanding. Nat. Rev. Mol. Cell Biol. 8, 451-463. (doi:10.1038/nrm2180)
2. Sluder G, Rieder CL. 1985 Centriole number and the reproductive capacity of spindle poles. J. Cell Biol. 100, 887-896. (doi:10.1083/jcb.100.3. 887)
3. Azimzadeh J, Bornens M. 2007 Structure and duplication of the centrosome. J. Cell Biol. 120, 2139-2142. (doi:10.1242/jcs.005231)
4. Bornens M, Azimzadeh J. 2007 Origin and evolution of the centrosome. Adv. Exp. Med. Biol. 607, 119-129. (doi:10.1007/978-0-387-74021-8_10)
5. Basto R, Lau J, Vinogradova T, Gardiol A, Woods CG, Khodjakov A, Raff JW. 2006 Flies without centrioles. Cell 125, 1375-1386. (doi:10.1016/j.cell.2006. 05.025)
6. Kalab P, Heald R. 2008 The RanGTP gradient: a GPS for the mitotic spindle. J. Cell Biol. 121, 1577-1586. (doi:10.1242/jcs.005959)
7. Yamashita YM, Jones DL, Fuller MT. 2003 Orientation of asymmetric stem cell division by the APC tumor suppressor and centrosome. Science 301, 1547-1550. (doi:10.1126/science. 1087795)
8. Yamashita YM et al. 2007 Asymmetric inheritance of mother versus daughter centrosome in stem cell division. Science 315, 518-521. (doi:10.1126/ science.1134910)
9. Wang X, Tsai J-W, Imai JH, Lian W-N, Vallee RB, Shi S-H. 2009 Asymmetric centrosome inheritance maintains neural progenitors in the neocortex. Nature 461, 947-955. (doi:10.1038/nature08435)
10. Sir JH, Putz M, Daly O, Morrison CG, Dunning M, Kilmartin JV, Gergely F. 2013 Loss of centrioles causes chromosomal instability in vertebrate somatic cells. J. Cell Biol. 13, 747-756. (doi:10. 1083/jcb.201309038)
11. Schockel L, Möckel M, Mayer B, Boos D, Stemmann O. 2011 Cleavage of cohesin rings coordinates the separation of centrioles and chromatids. Nat. Cell Biol. 13, 966-972. (doi:10.1038/ncb2280)
12. Matsuo K, Ohsumi K, Iwabuchi M, Kawamata T, Ono Y, Takahashi M. 2012 Kendrin is a novel substrate for separase involved in the licensing of centriole duplication. Curr. Biol. 22, 915-921. (doi:10.1016/j. cub.2012.03.048)
13. Thein KH, Kleylein-Sohn J, Nigg EA, Gruneberg U. 2007 Astrin is required for the maintenance of sister chromatid cohesion and centrosome integrity. J. Cell Biol. 178, 345-354. (doi:10.1083/jcb.200701163)
14. Nakamura A, Arai H, Fujita N. 2009 Centrosomal Aki1 and cohesin function in separase-regulated centriole disengagement. J. Cell Biol. 187, 607-614. (doi:10.1083/jcb.200906019)
15. Paintrand M, Moudjou M, Delacroix H, Bornens M. 1992 Centrosome organization and centriole architecture: their sensitivity to divalent cations. J. Struct. Biol. 108, 107-128. (doi:10.1016/1047-8477(92)90011-X)
16. Piel M, Meyer P, Khodjakov A, Rieder CL, Borners M. 2000 The respective contributions of the mother and daughter centrioles to centrosome activity and behavior in vertebrate cells. J. Cell Biol. 149, 317-330. (doi:10.1083/jcb.149.2.317)
17. Tsou MF, Stearns T. 2006 Mechanism limiting centrosome duplication to once per cell cycle. Nature 442, 947-951. (doi:10.1038/nature04985)
18. Wang WJ, Soni RK, Uryu K, Bryan Tsou M-F. 2011 The conversion of centrioles to centrosomes: essential coupling of duplication with segregation. J. Cell Biol. 193, 727-739. (doi:10.1083/jcb. 201101109)
19. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K. 1998 An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93, 1067-1076. (doi:10.1016/S0092-8674(00)81211-8)
20. Uhlmann F, Lottspeich F, Nasmyth K. 1999 Sisterchromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400, 37-42. (doi:10.1038/21831)
21. Chestukhin A, Pfeffer C, Milligan S, DeCaprio JA, Pellman D. 2003 Processing, localization, and requirement of human separase for normal anaphase progression. Proc. Natl Acad. Sci. USA 100, 4574-4579. (doi:10.1073/pnas.0730733100)
22. Tsou MF, Wang W-J, George KA, Uryu K, Stearns T, Jallepalli PV. 2009 Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev. Cell 17, 344-354. (doi:10.1016/j.devcel.2009.07.015)
23. Stemmann O, Zou H, Gerber SA, Gygi SP, Kirschner MW. 2001 Dual inhibition of sister chromatid separation at metaphase. Cell 107, 715-726. (doi:10.1016/S0092-8674(01)00603-1)
24. Tsang WY, Dynlacht BD. 2008 sSgo1, a guardian of centriole cohesion. Dev. Cell 14, 320-322. (doi:10. 1016/j.devcel.2008.02.008)
25. Wang X, Yang Y, Duan Q, Jiang N, Huang Y, Darzynkiewicz Z, Dai W. 2008 Sgo1, a major splice variant of Sgo1, functions in centriole cohesion where it is regulated by Plk1. Dev. Cell 14, 331-341. (doi:10.1016/j.devcel.2007.12.007)
26. Wong RW, Blobel G. 2008 Cohesin subunit SMC1 associates with mitotic microtubules at the spindle pole. Proc. Natl Acad. Sci. USA 105, 15 441-15 445. (doi:10.1073/pnas.0807660105)
27. Gregson HC, Schmiesing JA, Kim JS, Kobayashi T, Zhou S, Yokomori K. 2001 A potential role for human cohesin in mitotic spindle aster assembly. J. Biol. Chem. 276, 47 575-47 582. (doi:10.1074/ jbc.M103364200)
28. Kong X, Ball AR, Sonoda E, Feng J, Takeda S, Fukagawa T, Yen TJ, Yokomori K. 2009 Cohesin associates with spindle poles in a mitosis-specific manner and functions in spindle assembly in vertebrate cells. Mol. Biol. Cell 20, 1289-1301. (doi:10.1091/mbc.E08-04-0419)
29. Oliveira RA, Nasmyth K. 2013 Cohesin cleavage is insufficient for centriole disengagement in Drosophila. Curr. Biol. 23, R601-R603. (doi:10. 1016/j.cub.2013.04.003)
30. Cabral G, Sanegre Sans S, Cowan CR, Dammermann A. 2013 Multiple mechanisms contribute to centriole separation in C. elegans. Curr. Biol. 23, 1380-1387. (doi:10.1016/j.cub.2013.06.043)
31. Mayor T, Stierhof Y-D, Tanaka K, Fry AM, Nigg EA. 2000 The centrosomal protein C-Nap1 is required for cell cycle-regulated centrosome cohesion. J. Cell Biol. 151, 837-846. (doi:10.1083/jcb.151.4.837)
32. Yang J, Liu X, Yue G, Adamian M, Bulgakov O, Li T. 2002 Rootletin, a novel coiled-coil protein, is a structural component of the ciliary rootlet. J. Cell Biol. 159, 431-440. (doi:10.1083/jcb. 200207153)
33. Yang J, Adamian M, Li T. 2006 Rootletin interacts with C-Nap1 and may function as a physical linker between the pair of centrioles/basal bodies in cells. Mol. Biol. Cell 17, 1033-1040. (doi:10.1091/mbc. E05-10-0943)
34. Bahe S, Stierhof YD, Wilkinson CJ, Leiss F, Nigg EA. 2005 Rootletin forms centriole-associated filaments and functions in centrosome cohesion. J. Cell Biol. 171, 27-33. (doi:10.1083/jcb.200504107)
35. Graser S, Stierhof YD, Nigg EA. 2007 Cep68 and Cep215 (Cdk5rap2) are required for centrosome cohesion. J. Cell Biol. 120, 4321-4331. (doi:10. 1242/jcs.020248)
36. Lin YC, Chang C-W, Hsu W-B, Tang C-JC, Lin Y-N, Chou E-J, Wu C-T, Tang TK. 2013 Human microcephaly protein CEP135 binds to hSAS-6 and CPAP, and is required for centriole assembly. EMBO J. 32, 1141-1154. (doi:10.1038/emboj.2013.56)
37. Kim K, Lee S, Chang J, Rhee K. 2008 A novel function of CEP135 as a platform protein of C-NAP1 for its centriolar localization. Exp. Cell Res. 314, 3692-3700. (doi:10.1016/j.yexcr.2008.09.016)
38. Barrera JA, Kao L-R, Hammer RE, Seemann J, Fuchs JL, Megraw TL. 2010 CDK5RAP2 regulates centriole engagement and cohesion in mice. Dev. Cell 18, 913-926. (doi:10.1016/j.devcel.2010.05.017)
39. He R, Huang N, Bao Y, Zhou H, Teng J, Chen J. 2013 LRRC45 is a centrosome linker component required for centrosome cohesion. Cell Rep. 4, 1100-1107. (doi:10.1016/j.celrep.2013.08.005)
40. Fogeron ML et al. 2013 LGALS3BP regulates centriole biogenesis and centrosome hypertrophy in cancer cells. Nat. Commun. 4, 1531. (doi:10.1038/ ncomms2517)
41. Fry AM, Mayor T, Meraldi P, Stierhof YD, Tanaka K, Nigg EA. 1998 C-Nap1, a novel centrosomal coiled-coil protein and candidate substrate of the cell cycle-regulated protein kinase Nek2. J. Cell Biol. 141, 1563-1574. (doi:10.1083/jcb.141.7.1563)
42. Chevrier V, Piel M, Collomb N, Saoudi Y, Frank R, Paintrand M, Narumiya S, Bornens M, Job D. 2002 The Rho-associated protein kinase p160ROCK is required for centrosome positioning. J. Cell Biol. 157, 807-817. (doi:10.1083/jcb.200203034)
43. Abal M, Piel M, Bouckson-Castaing V, Mogensen M, Sibarita JB, Bornens M. 2002 Microtubule release from the centrosome in migrating cells. J. Cell Biol. 159, 731-737. (doi:10.1083/jcb. 200207076)
44. Hurtado L, Caballero C, Gavilan MP, Cardenas J, Bornens M, Rios RM. 2011 Disconnecting the Golgi ribbon from the centrosome prevents directional cell migration and ciliogenesis. J. Cell Biol. 193, 917-933. (doi:10.1083/jcb.201011014)
45. Bolhy S, Bouhlel I, Dultz E, Nayak T, Zuccolo M, Gatti X, Vallee R, Ellenberg J, Doye V. 2011 A Nup133-dependent NPC-anchored network tethers centrosomes to the nuclear envelope in prophase. J. Cell Biol. 192, 855-871. (doi:10.1083/jcb. 201007118)
46. Splinter D et al. 2010 Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry. PLoS Biol. 8, e1000350. (doi:10.1371/ journal.pbio.1000350)
47. Stinchcombe JC, Majorovits E, Bossi G, Fuller S, Griffiths GM. 2006 Centrosome polarization delivers secretory granules to the immunological synapse. Nature 443, 462-465. (doi:10.1038/ nature05071)
48. Starr DA. 2011 KASH and SUN proteins. Curr. Biol. 21, R414-R415. (doi:10.1016/j.cub.2011.04.022)
49. Wang W et al. 2012 Structural insights into SUNKASH complexes across the nuclear envelope. Cell Res 22, 1440-1452. (doi:10.1038/cr.2012.126)
50. Burke B. 2012 It takes KASH to hitch to the SUN. Cell 149, 961-963. (doi:10.1016/j.cell.2012.05.004)
51. Hiraoka Y, Dernburg AF. 2009 The SUN rises on meiotic chromosome dynamics. Dev. Cell 17, 598-605. (doi:10.1016/j.devcel.2009.10.014)
52. Razafsky D, Hodzic D. 2009 Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections. J. Cell Biol. 186, 461-472. (doi:10. 1083/jcb.200906068)
53. Fridkin A, Penkner A, Jantsch V, Gruenbaum Y. 2009 SUN-domain and KASH-domain proteins during development, meiosis and disease. Cell Mol. Life Sci. 66, 1518-1533. (doi:10.1007/s00018-008-8713-y)
54. Zhang X, Lei K, Yuan X, Wu X, Zhuang Y, Xu T, Xu R, Han M. 2009 SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice. Neuron 64, 173-187. (doi:10.1016/j.neuron. 2009.08.018)
55. Leo M, Santino D, Tikhonenko I, Magidson V, Khodjakov A, Koonce MP. 2012 Rules of engagement: centrosome-nuclear connections in a closed mitotic system. Biol. Open 1, 1111-1117. (doi:10.1242/bio.20122188)
56. Tikhonenko I, Magidson V, Gräf R, Khodjakov A, Koonce MP. 2013 A kinesin-mediated mechanism that couples centrosomes to nuclei. Cell Mol. Life Sci. 70, 1285-1296. (doi:10.1007/s00018-012-1205-0)
57. Faragher AJ, Fry AM. 2003 Nek2A kinase stimulates centrosome disjunction and is required for formation of bipolar mitotic spindles. Mol. Biol. Cell 14, 2876-2889. (doi:10.1091/mbc.E03-02-0108)
58. Mardin BR, Agircan FG, Lange C, Schiebel E. 2011 Plk1 controls the Nek2A-PP1gamma antagonism in centrosome disjunction. Curr. Biol. 21, 1145-1151. (doi:10.1016/j.cub.2011.05.047)
59. Rapali P, Szenes Á, Radnai L, Bakos A, Pál G, Nyitray L. 2011 DYNLL/LC8: a light chain subunit of the dynein motor complex and beyond. FEBS J. 278, 2980-2996. (doi:10.1111/j.1742-4658.2011. 08254.x)
60. Regue L, Sdelci S, Bertran MT, Caelles C, Reverter D, Roig J. 2011 DYNLL/LC8 protein controls signal transduction through the Nek9/Nek6 signaling module by regulating Nek6 binding to Nek9. J. Biol. Chem. 286, 18 118-18 129. (doi:10.1074/jbc.M110. 209080)
61. Blangy A, Lane HA, d'Hérin P, Harper M, Kress M, Niggt EA. 1995 Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo. Cell 83, 1159-1169. (doi:10. 1016/0092-8674(95)90142-6)
62. Blangy A, Arnaud L, Nigg EA. 1997 Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor HsEg5 to the dynactin subunit p150. J. Biol. Chem. 272, 19 418-19 424. (doi:10. 1074/jbc.272.31.19418)
63. Hames RS, Wattam SL, Yamano H, Bacchieri R, Fry AM. 2001 APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box. EMBO J. 20, 7117-7127. (doi:10.1093/emboj/20.24.7117)
64. Fletcher L, Cerniglia GJ, Nigg EA, Yen TJ, Muschel RJ. 2004 Inhibition of centrosome separation after DNA damage: a role for Nek2. Radiat. Res. 162, 128-135. (doi:10.1667/RR3211)
65. Helps NR, Luo X, Barker HM, Cohen PTW. 2000 NIMA-related kinase 2 (Nek2), a cell-cycle-regulated protein kinase localized to centrosomes, is complexed to protein phosphatase 1. Biochem J. 349, 509-518. (doi:10.1042/0264-6021:3490509)
66. Yu FX et al. 2013 Protein kinase A activates the Hippo pathway to modulate cell proliferation and differentiation. Genes Dev. 27, 1223-1232. (doi:10. 1101/gad.219402.113)
67. Mardin BR, Lange C, Baxter JE, Hardy T, Scholz SR, Fry AM, Schiebel E. 2010 Components of the Hippo pathway cooperate with Nek2 kinase to regulate centrosome disjunction. Nat. Cell Biol. 12, 1166-1176. (doi:10.1038/ncb2120)
68. Hergovich A, Cornils H, Hemmings BA. 2008 Mammalian NDR protein kinases: from regulation to a role in centrosome duplication. Biochim. Biophys. Acta 1784, 3-15. (doi:10.1016/j.bbapap. 2007.07.017)
69. Smith E et al. 2011 Differential control of Eg5-dependent centrosome separation by Plk1 and Cdk1. EMBO J. 30, 2233-2245. (doi:10.1038/ emboj.2011.120)
70. Ferenz NP, Gable A, Wadsworth P. 2010 Mitotic functions of kinesin-5. Semin. Cell Dev. Biol. 21, 255-259. (doi:10.1016/j.semcdb.2010.01.019)
71. Sawin KE, LeGuellec K, Philippe M, Mitchison TJ. 1992 Mitotic spindle organization by a plus-enddirected microtubule motor. Nature 359, 540-543. (doi:10.1038/359540a0)
72. Cole DG, Saxton WM, Sheehan KB, Scholey JM. 1994 A 'slow' homotetrameric kinesin-related motor protein purified from Drosophila embryos. J. Biol. Chem. 269, 22 913-22 916.
73. Kashina AS, Baskin RJ, Cole DG, Wedaman KP, Saxton WM, Scholey JM. 1996 A bipolar kinesin. Nature 379, 270-272. (doi:10.1038/379270a0)
74. Kapitein LC, Peterman EJG, Kwok BH, Kim JH, Kapoor TM, Schmidt CF. 2005 The bipolar mitotic kinesin Eg5 moves on both microtubules that it crosslinks. Nature 435, 114-118. (doi:10.1038/ nature03503)
75. Bertran MT, Sdelci S, Regué L, Avruch J, Caelles C, Roig J. 2011 Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J. 30, 2634-2647. (doi:10. 1038/emboj.2011.179)
76. Waters JC, Cole RW, Rieder CL. 1993 The forceproducing mechanism for centrosome separation during spindle formation in vertebrates is intrinsic to each aster. J. Cell Biol. 122, 361-372. (doi:10. 1083/jcb.122.2.361)
77. Tanenbaum ME, Medema RH. 2010 Mechanisms of centrosome separation and bipolar spindle assembly. Dev. Cell 19, 797-806. (doi:10.1016/j. devcel.2010.11.011)
78. Gaglio T, Saredi A, Bingham JB, Hasbani MJ, Gill SR, Schroer TA, Compton DA. 1996 Opposing motor activities are required for the organization of the mammalian mitotic spindle pole. J. Cell Biol. 135, 399-414. (doi:10.1083/jcb.135.2.399)
79. Tanenbaum ME, Macurek L, Galjart N, Medema RH. 2008 Dynein, Lis1 and CLIP-170 counteract Eg5-dependent centrosome separation during bipolar spindle assembly. EMBO J. 27, 3235-3245. (doi:10. 1038/emboj.2008.242)
80. Gonczy P, Pichler S, Kirkham M, Hyman AA. 1999 Cytoplasmic dynein is required for distinct aspects of MTOC positioning, including centrosome separation, in the one cell stage Caenorhabditis elegans embryo. J. Cell Biol. 147, 135-150. (doi:10. 1083/jcb.147.1.135)
81. Pereira AL et al. 2006 Mammalian CLASP1 and CLASP2 cooperate to ensure mitotic fidelity by regulating spindle and kinetochore function. Mol. Biol. Cell 17, 4526-4542. (doi:10.1091/mbc.E06-07-0579)
82. Florian S, Mayer TU. 2012 The functional antagonism between Eg5 and dynein in spindle bipolarization is not compatible with a simple pushpull model. Cell Rep. 1, 408-416. (doi:10.1016/j. celrep.2012.03.006)
83. Raaijmakers JA, van Heesbeen RGHP, Meaders JL, Geers EF, Fernandez-Garcia B, Medema RH, Tanenbaum ME. 2012 Nuclear envelope-associated dynein drives prophase centrosome separation and enables Eg5-independent bipolar spindle formation. EMBO J. 31, 4179-4190. (doi:10.1038/emboj. 2012.272)
84. Vanneste D, Ferreira V, Vernos I. 2011 Chromokinesins: localization-dependent functions and regulation during cell division. Biochem. Soc. Trans. 39, 1154-1160. (doi:10.1042/BST0391154)
85. Tanenbaum ME, Macurek L, Janssen A, Geers EF, Alvarez-Fernández M, Medema R. 2009 Kif15 cooperates with Eg5 to promote bipolar spindle assembly. Curr. Biol. 19, 1703-1711. (doi:10.1016/ j.cub.2009.08.027)
86. Boleti H, Karsenti E, Vernos I. 1996 Xklp2, a novel Xenopus centrosomal kinesin-like protein required for centrosome separation during mitosis. Cell 84, 49-59. (doi:10.1016/S0092-8674(00)80992-7)
87. Sturgill EG, Ohi R. 2013 Kinesin-12 differentially affects spindle assembly depending on its microtubule substrate. Curr. Biol. 23, 1280-1290. (doi:10.1016/j.cub.2013.05.043)
88. Thery M, Racine V, Pépin A, Piel M, Chen Y, Sibarita JB, Bornens M. 2005 The extracellular matrix guides the orientation of the cell division axis. Nat. Cell Biol. 7, 947-953. (doi:10.1038/ncb1307)
89. Magidson V, O'Connell CB, Lonĉarek J, Paul R, Mogilner A, Khodjakov A. 2011 The spatial arrangement of chromosomes during prometaphase facilitates spindle assembly. Cell 146, 555-567. (doi:10.1016/j.cell.2011.07.012)
90. Toso A, Winter JR, Garrod AJ, Amaro AC, Meraldi P, McAinsh AD. 2009 Kinetochore-generated pushing forces separate centrosomes during bipolar spindle assembly. J. Cell Biol. 184, 365-372. (doi:10.1083/ jcb.200809055)
91. Sherline P, Mascardo R. 1982 Epidermal growth factor-induced centrosomal separation: mechanism and relationship to mitogenesis. J. Cell Biol. 95, 316-322. (doi:10.1083/jcb.95.1.316)
92. Mardin BR, Isokane M, Cosenza MR, Krämer A, Ellenberg J, Fry AM, Schiebel E. 2013 EGF-induced centrosome separation promotes mitotic progression and cell survival. Dev. Cell 25, 229-240. (doi:10. 1016/j.devcel.2013.03.012)
93. Silkworth WT, Nardi IK, Paul R, Mogilner A, Cimini D. 2012 Timing of centrosome separation is important for accurate chromosome segregation. Mol. Biol. Cell 23, 401-411. (doi:10.1091/mbc.E11-02-0095)
94. Kaseda K, McAinsh AD, Cross RA. 2012 Dual pathway spindle assembly increases both the speed and the fidelity of mitosis. Biol. Open 1, 12-18. (doi:10.1242/bio.2011012)
95. So CH, Michal A, Komolov KE, Luo J, Benovic JL. 2013 G protein-coupled receptor kinase 2 (GRK2) is localized to centrosomes and mediates epidermal growth factor-promoted centrosomal separation. Mol. Biol. Cell 24, 2795-2806. (doi:10.1091/mbc. E13-01-0013)
96. Mazzorana M, Montoya G, Mortuza GB. 2011 The centrosome: a target for cancer therapy. Curr. Cancer Drug Targets 11, 600-612. (doi:10.2174/ 156800911795655949)
97. Bergnes G, Brejc K, Belmont L. 2005 Mitotic kinesins: prospects for antimitotic drug discovery. Curr. Top. Med. Chem. 5, 127-145. (doi:10.2174/ 1568026053507697)
98. Kim KB et al. 2013 Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAFmutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J. Clin. Oncol. 31, 482-489. (doi:10.1200/JCO.2012.43.5966)
99. Flaherty KT et al. 2012 Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694-1703. (doi:10.1056/ NEJMoa1210093)