BubR1 kinase: Protection against aneuploidy and premature aging

Trends in Molecular Medicine

Volumn 21, Issue 6, 2015, Pages 364-372

  Kapanidou, Maria ^a   Lee, Semin ^b   Bolanos Garcia, Victor M ^a  

^a OXFORD BROOKES UNIVERSITY   (United Kingdom)

^b Harvard Medical School Center for Biomedical Informatics   (United States)

Author keywords

BubR1; Chromosome segregation; Genome instability; Kinetochore; Premature aging; Spindle assembly checkpoint (SAC)

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 9 CYCLOPENTYL 2 [2 METHOXY 4 (1 METHYL 4 PIPERIDINYLOXY)ANILINO] 7 METHYL 7H PURIN 8(9H) ONE; BUB1 RELATED PROTEIN; PF 3814735; BUB1 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE;

AGING; ANEUPLOIDY; AUTOSOMAL RECESSIVE DISORDER; ENZYME ACTIVE SITE; GENE MUTATION; GENETIC SCREENING; HUMAN; INFERTILITY; KINETOCHORE MICROTUBULE; M PHASE CELL CYCLE CHECKPOINT; MOSAIC VARIEGATED ANEUPLOIDY; NONHUMAN; PREMATURE AGING; PROTECTION; PROTEIN FUNCTION; PROTEIN PROCESSING; REGULATORY MECHANISM; REVIEW; SENESCENCE; TETRATRICOPEPTIDE REPEAT; ANIMAL; CHEMICAL STRUCTURE; CHEMISTRY; ENZYMOLOGY; GENETICS; GENOMIC INSTABILITY; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; NEOPLASMS;

EUKARYOTA; MUS;

AGING, PREMATURE; ANEUPLOIDY; ANIMALS; GENOMIC INSTABILITY; HUMANS; M PHASE CELL CYCLE CHECKPOINTS; MODELS, MOLECULAR; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASMS; PROTEIN-SERINE-THREONINE KINASES;

EID: 84930541259     PISSN: 14714914     EISSN: 1471499X     Source Type: Journal    
DOI: 10.1016/j.molmed.2015.04.003     Document Type: Review

References (89)

1. Foley E.A., Kapoor T.M. Microtubule attachment and spindle assembly checkpoint signalling at the kinetochore. Nat. Rev. Mol. Cell Biol. 2013, 14:25-37.
2. Musacchio A. Spindle assembly checkpoint: the third decade. Philos. Trans. R. Soc. Lond. B: Biol. Sci. 2011, 366:3595-3604.
3. Sacristan C., Kops G.J. Joined at the hip: kinetochores, microtubules, and spindle assembly checkpoint signaling. Trends Cell Biol. 2015, 25:21-28.
4. Przewloka M.R., Glover D.M. The kinetochore and the centromere: a working long distance relationship. Annu. Rev. Genet. 2009, 43:439-465.
5. Hauf S. The spindle assembly checkpoint: progress and persistent puzzles. Biochem. Soc. Trans. 2013, 41:1755-1760.
6. Hoyt M.A., et al. S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. Cell 1991, 66:507-517.
7. Yao Y., Dai W. Mitotic checkpoint control and chromatin remodeling. Front. Biosci. 2012, 17:976-983.
8. Silva P.M., et al. Dynein-dependent transport of spindle assembly checkpoint proteins off kinetochores toward spindle poles. FEBS Lett. 2014, 588:3265-3273.
9. Boyarchuk Y., et al. Bub1 is essential for assembly of the functional inner centromere. J. Cell Biol. 2007, 176:919-928.
10. Tipton A.R., et al. Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex. J. Biol. Chem. 2013, 288:35149-35158.
11. Hewitt L., et al. Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1-C-Mad2 core complex. J. Cell Biol. 2010, 190:25-34.
12. London N., Biggins S. Mad1 kinetochore recruitment by Mps1-mediated phosphorylation of Bub1 signals the spindle checkpoint. Genes Dev. 2014, 28:140-152.
13. Zich J., et al. Kinase activity of fission yeast Mph1 is required for Mad2 and Mad3 to stably bind the anaphase promoting complex. Curr. Biol. 2012, 22:296-301.
14. Conde C., et al. Drosophila Polo regulates the spindle assembly checkpoint through Mps1-dependent BubR1 phosphorylation. EMBO J. 2013, 32:1761-1777.
15. Huang H., et al. Phosphorylation sites in BubR1 that regulate kinetochore attachment, tension, and mitotic exit. J. Cell Biol. 2008, 183:667-680.
16. Elowe S., et al. Tension-sensitive Plk1 phosphorylation on BubR1 regulates the stability of kinetochore microtubule interactions. Genes Dev. 2007, 21:2205-2219.
17. Bolanos-Garcia V.M., Blundell T.L. BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends Biochem. Sci. 2011, 36:141-150.
18. Ricke R.M., et al. Whole chromosome instability and cancer: a complex relationship. Trends Genet. 2008, 24:457-466.
19. Chao W.C.H., et al. Structure of the mitotic checkpoint complex. Nature 2012, 484:208-213.
20. Sczaniecka M., et al. The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C). J. Biol. Chem. 2008, 283:23039-23047.
21. Burton J.L., Solomon M.J. Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes Dev. 2007, 21:655-667.
22. King E.M., et al. Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint. PLoS ONE 2007, 2:e342.
23. Lischetti T., et al. The internal Cdc20 binding site in BubR1 facilitates both spindle assembly checkpoint signaling and silencing. Nat. Commun. 2014, 5:5563.
24. Tang Z., et al. MAD2-independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev. Cell 2001, 1:227-237.
25. Di Fiore B., et al. The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators. Dev. Cell 2015, 32:358-372.
26. Diaz-Martinez L.A., et al. The Cdc20-binding Phe box of the spindle checkpoint protein BubR1 maintains the mitotic checkpoint complex during mitosis. J. Biol. Chem. 2015, 290:2431-2443.
27. Larsen N.A., et al. Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Proc. Natl. Acad. Sci. U.S.A. 2007, 104:1201-1206.
28. London N., et al. Phosphoregulation of Spc105 by Mps1 and PP1 regulates Bub1 localization to kinetochores. Curr. Biol. 2012, 22:900-906.
29. Primorac I., et al. Bub3 reads phosphorylated MELT repeats to promote spindle assembly checkpoint signaling. Elife 2013, 2:e01030.
30. Shepperd L.A., et al. Phosphodependent recruitment of Bub1 and Bub3 to Spc7/KNL1 by Mph1 kinase maintains the spindle checkpoint. Curr. Biol. 2012, 22:891-899.
31. Yamagishi Y., et al. MPS1/Mph1 phosphorylates the kinetochore protein KNL1/Spc7 to recruit SAC components. Nat. Cell Biol. 2012, 14:746-752.
32. Krenn V., et al. Structural analysis reveals features of the spindle checkpoint kinase Bub1-kinetochore subunit Knl1 interaction. J. Cell Biol. 2012, 196:451-467.
33. Bolanos-Garcia V.M., et al. Structure of a Blinkin-BUBR1 complex reveals an interaction crucial for kinetochore-mitotic checkpoint regulation via an unanticipated binding Site. Structure 2011, 19:1691-1700.
34. Malureanu L.A., et al. BubR1N terminus acts as a soluble inhibitor of cyclin B degradation by APC/C(Cdc20) in interphase. Dev. Cell 2009, 16:118-131.
35. Suijkerbuijk S.J., et al. Molecular causes for BUBR1 dysfunction in the human cancer predisposition syndrome mosaic variegated aneuploidy. Cancer Res. 2010, 70:4891-4900.
36. Mao Y., et al. Activating and silencing the mitotic checkpoint through CENP-E-dependent activation/inactivation of BubR1. Cell 2003, 114:87-98.
37. Zhang J., et al. BubR1 and APC/EB1 cooperate to maintain metaphase chromosome alignment. J. Cell Biol. 2007, 178:773-784.
38. Huang H., Yen T.J. BubR1 is an effector of multiple mitotic kinases that specifies kinetochore microtubule attachments and checkpoint. Cell Cycle 2009, 8:1164-1167.
39. Suijkerbuijk S.J., et al. The vertebrate mitotic checkpoint protein BUBR1 is an unusual pseudokinase. Dev. Cell 2012, 22:1321-1329.
40. Fang Y., et al. BubR1 is involved in regulation of DNA damage responses. Oncogene 2006, 25:3598-3605.
41. Miyamoto T., et al. Insufficiency of BUBR1, a mitotic spindle checkpoint regulator, causes impaired ciliogenesis in vertebrates. Hum. Mol. Genet. 2011, 20:2058-2070.
42. Baker D.J., et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat. Genet. 2004, 36:744-749.
43. Rahmani Z., et al. Separating the spindle, checkpoint, and timer functions of BubR1. J. Cell Biol. 2009, 187:597-605.
44. Wong K.O., Fang G. Cdk1 phosphorylation of BubR1 controls spindle checkpoint arrest and Plk1-mediated formation of the 3F3/2 epitope. J. Cell Biol. 2007, 179:611-617.
45. Klebig C., et al. Bub1 regulates chromosome segregation in a kinetochore-independent manner. J. Cell Biol. 2009, 185:841-858.
46. Zich J., Hardwick K.G. Getting down to the phosphorylated 'nuts and bolts' of spindle checkpoint signalling. Trends Biochem. Sci. 2010, 35:18-27.
47. Kim P.M., et al. Relating three-dimensional structures to protein networks provides evolutionary insights. Science 2006, 314:1938-1941.
48. Jia L., et al. Tracking spindle checkpoint signals from kinetochores to APC/C. Trends Biochem. Sci. 2013, 38:302-311.
49. Lee S., Bolanos-Garcia V.M. The dynamics of signal amplification by macromolecular assemblies for the control of chromosome segregation. Front. Physiol. 2014, 5:368.
50. Choi E., et al. BubR1 acetylation at prometaphase is required for modulating APC/C activity and timing of mitosis. EMBO J. 2009, 28:2077-2089.
51. Yekezare M., Pines J. Escaping the firing squad: acetylation of BubR1 protects it from degradation in checkpoint cells. EMBO J. 2009, 28:1991-1993.
52. Suematsu T., et al. Deacetylation of the mitotic checkpoint protein BubR1 at lysine 250 by SIRT2 and subsequent effects on BubR1 degradation during the prometaphase/anaphase transition. Biochem. Biophys. Res. Commun. 2014, 453:588-594.
53. North B.J., et al. SIRT2 induces the checkpoint kinase BubR1 to increase lifespan. EMBO J. 2014, 33:1438-1453.
54. Baker D.J., et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479:232-236.
55. Baker D.J., et al. The mitotic checkpoint in cancer and aging: what have mice taught us?. Curr. Opin. Cell Biol. 2005, 17:583-589.
56. Horvath S., et al. Accelerated epigenetic aging in Down syndrome. Aging Cell 2015, 14:491-495.
57. Belancio V.P., et al. The aging clock and circadian control of metabolism and genome stability. Front. Genet. 2015, 5:455.
58. Matsumoto T., et al. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 2007, 38:1050-1056.
59. Hartman T.K., et al. Mutant mice with small amounts of BubR1 display accelerated age-related gliosis. Neurobiol. Aging 2007, 28:921-927.
60. Hanks S., et al. Constitutional aneuploidy and cancer predisposition caused by biallelic mutations in BUB1B. Nat. Genet. 2004, 36:1159-1161.
61. Lengauer C., Wang Z. From spindle checkpoint to cancer. Nat. Genet. 2004, 36:1144-1145.
62. Kajii T., et al. Mosaic variegated aneuploidy with multiple congenital abnormalities: homozygosity for total premature chromatid separation trait. Am. J. Med. Genet. 1998, 78:245-249.
63. Furukawa T., et al. Cystic partially differentiated nephroblastoma, embryonal rhabdomyosarcoma, and multiple congenital anomalies associated with variegated mosaic aneuploidy and premature centromere division: a case report. J. Pediatr. Hematol. Oncol. 2003, 25:896-899.
64. Wijshake T., et al. Reduced life- and healthspan in mice carrying a mono-allelic BubR1 MVA mutation. PLoS Genet. 2012, 8:e1003138.
65. Baker D.J., et al. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nat. Cell Biol. 2013, 15:96-102.
66. Chan K.S., et al. Mitosis-targeted anti-cancer therapies: where they stand. Cell Death Dis. 2012, 3:e411.
67. Miao S., et al. Synuclein γ compromises spindle assembly checkpoint and renders resistance to antimicrotubule drugs. Mol. Cancer Ther. 2014, 13:699-713.
68. Laufer R., et al. Discovery of inhibitors of the mitotic kinase TTK based on N-(3-(3-sulfamoylphenyl)-1H-indazol-5-yl)-acetamides and carboxamides. Bioorg. Med. Chem. 2014, 22:4968-4997.
69. Tsai C.J., Nussinov R. The molecular basis of targeting protein kinases in cancer therapeutics. Semin. Cancer Biol. 2013, 23:235-242.
70. Frey A. Cdc20 turnover rate: a key determinant in cancer patient response to anti-mitotic therapies?. Bioessays 2013, 35:762.
71. Lawson A.D.G. Antibody-enabled small-molecule drug discovery. Nat. Rev. Drug Discov. 2012, 11:519-525.
72. Block P., et al. Strategies to search and design stabilizers of protein-protein interactions: a feasibility study. Proteins 2007, 68:170-186.
73. Higueruelo A.P., et al. Protein-protein interactions as druggable targets: recent technological advances. Curr. Opin. Pharmacol. 2013, 13:791-796.
74. Kruse T., et al. Direct binding between BubR1 and B56-PP2A phosphatase complexes regulate mitotic progression. J. Cell Sci. 2013, 126:1086-1092.
75. Xu P., et al. BUBR1 recruits PP2A via the B56 family of targeting subunits to promote chromosome congression. Biol. Open 2013, 2:479-486.
76. Xu P., et al. B56-PP2A regulates motor dynamics for mitotic chromosome alignment. J. Cell Sci. 2014, 127:4567-4573.
77. Naylor R.M., et al. Senescent cells: a novel therapeutic target for aging and age-related diseases. Clin. Pharmacol. Ther. 2013, 93:105-116.
78. Park I., et al. Loss of BubR1 acetylation causes defects in spindle assembly checkpoint signaling and promotes tumor formation. J. Cell Biol. 2013, 202:295-309.
79. Cahill D.P., et al. Mutations of mitotic checkpoint genes in human cancers. Nature 1998, 392:300-303.
80. Ohshima K., et al. Mutation analysis of mitotic checkpoint genes (hBUB1 and hBUBR1) and microsatellite instability in adult T-cell leukemia/lymphoma. Cancer Lett. 2000, 158:141-150.
81. Matsuura S., et al. Monoallelic BUB1B mutations and defective mitotic-spindle checkpoint in seven families with premature chromatid separation (PCS) syndrome. Am. J. Med. Genet. A 2006, 140:358-367.
82. Cahill D.P., et al. Characterization of MAD2B and other mitotic spindle checkpoint genes. Genomics 1999, 58:181-187.
83. Saeki A., et al. Frequent Impairment of the spindle assembly checkpoint in hepatocellular carcinoma. Cancer 2002, 94:2047-2054.
84. Reis R.M., et al. Mutation analysis of hBUB1, hBUBR1 and hBUB3 genes in glioblastomas. Acta Neuropathol. 2001, 101:297-304.
85. Myrie K.A., et al. Mutation and expression analysis of human BUB1 and BUB1B in aneuploid breast cancer cell lines. Cancer Lett. 2000, 152:193-199.
86. Hanks S., et al. Comparative genomic hybridization and BUB1B mutation analyses in childhood cancers associated with mosaic variegated aneuploidy syndrome. Cancer Lett. 2006, 239:234-238.
87. Plaja A., et al. Variegated aneuploidy related to premature centromere division (PCD) is expressed in vivo and is a cancer-prone disease. Am. J. Med. Genet. 2001, 98:216-223.
88. Sunyaev S., et al. Prediction of deleterious human alleles. Hum. Mol. Genet. 2001, 10:591-597.
89. Limwongse C., et al. Child with mosaic variegated aneuploidy and embryonal rhabdomyosarcoma. Am. J. Med. Genet. 1999, 82:20-24.