Centromere localization of INCENP-aurora B is sufficient to support spindle checkpoint function

被引:26
作者
Becker, Markus [1 ]
Stolz, Ailine [1 ]
Ertych, Norman [1 ]
Bastians, Holger [1 ]
机构
[1] Univ Marburg, Inst Mol Biol & Tumor Res IMT, Marburg, Germany
关键词
cell cycle; mitosis; chromosomal passenger complex; chromosome alignment; CHROMOSOMAL PASSENGER COMPLEX; UNATTACHED KINETOCHORES; MICROTUBULE DYNAMICS; ASSEMBLY CHECKPOINT; MITOTIC SPINDLE; CLEAVAGE FURROW; SURVIVIN; KINASE; CELLS; INHIBITION;
D O I
10.4161/cc.9.7.11177
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During mitosis, the chromosomal passenger complex (CpC) comprising the Aurora B kinase, INCeNp, survivin and borealin is essential for correcting non-bipolar chromosome attachments and for cytokinesis. In addition, the CpC might fullfil a role in the mitotic spindle assembly checkpoint (SAC), but this activity might be related to its role in correcting non-bipolar chromosome attachments. Here, we demonstrate that treatment of mitotic cells with the antibiotic actinomycin D causes a displacement of an intact and active CpC from centromeres onto chromosome arms, which results in chromosome misalignment, cytokinesis failure and SAC override, but still preserves histone H3 phosphorylation on chromosome arms. this surprising and unique scenario allows the reconstitution of endogenous Aurora B at centromeres/inner kinetochores by expressing a Cenp-B-INCeNp fusion protein. We find that although the selective recruitment of endogenous Aurora B to centromeres/inner kinetochores is not sufficient to restore chromosome alignment and cytokinesis, it can restore Cenp-A phosphorylation at kinetochores, BubR1 recruitment to kinetochores and SAC activity after spindle disruption. these results indicate that INCeNp-Aurora B localized at centromeres/inner kinetochores is sufficient to mediate SAC activity upon spindle disruption.
引用
收藏
页码:1360 / 1372
页数:13
相关论文
共 41 条
[1]   INCENP binds the Aurora-related kinase AIRK2 and is required to target it to chromosomes, the central spindle and cleavage furrow [J].
Adams, RR ;
Wheatley, SP ;
Gouldsworthy, AM ;
Kandels-Lewis, SE ;
Carmena, M ;
Smythe, C ;
Gerloff, DL ;
Earnshaw, WD .
CURRENT BIOLOGY, 2000, 10 (17) :1075-1078
[2]   The spindle checkpoint, aneuploidy, and cancer [J].
Bharadwaj, R ;
Yu, HT .
ONCOGENE, 2004, 23 (11) :2016-2027
[3]   Survivin is required for stable checkpoint activation in taxol-treated HeLa cells [J].
Carvalho, A ;
Carmena, M ;
Sambade, C ;
Earnshaw, WC ;
Wheatley, SP .
JOURNAL OF CELL SCIENCE, 2003, 116 (14) :2987-2998
[4]   Phospho-regulation of kinetochore-microtubule attachments by the aurora kinase Ipl1p [J].
Cheeseman, LM ;
Anderson, S ;
Jwa, M ;
Green, EM ;
Kang, JS ;
Yates, JR ;
Chan, CSM ;
Drubin, DG ;
Barnes, G .
CELL, 2002, 111 (02) :163-172
[5]   Kinetochore microtubule dynamics and attachment stability are regulated by Hec1 [J].
DeLuca, Jennifer G. ;
Gall, Walter E. ;
Ciferri, Claudio ;
Cimini, Daniela ;
Musacchio, Andrea ;
Salmon, E. D. .
CELL, 2006, 127 (05) :969-982
[6]   Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores [J].
Ditchfield, C ;
Johnson, VL ;
Tighe, A ;
Ellston, R ;
Haworth, C ;
Johnson, T ;
Mortlock, A ;
Keen, N ;
Taylor, SS .
JOURNAL OF CELL BIOLOGY, 2003, 161 (02) :267-280
[7]   Chromosomal proteins and cytokinesis: Patterns of cleavage furrow formation and inner centromere protein positioning in mitotic heterokaryons and mid-anaphase cells [J].
Eckley, DM ;
Ainsztein, AM ;
Mackay, AM ;
Goldberg, IG ;
Earnshaw, WC .
JOURNAL OF CELL BIOLOGY, 1997, 136 (06) :1169-1183
[8]   Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle [J].
Gassmann, R ;
Carvalho, A ;
Henzing, AJ ;
Ruchaud, S ;
Hudson, DE ;
Honda, R ;
Nigg, EA ;
Gerloff, DL ;
Earnshaw, WC .
JOURNAL OF CELL BIOLOGY, 2004, 166 (02) :179-191
[9]   The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint [J].
Hauf, S ;
Cole, RW ;
LaTerra, S ;
Zimmer, C ;
Schnapp, G ;
Walter, R ;
Heckel, A ;
van Meel, J ;
Rieder, CL ;
Peters, JM .
JOURNAL OF CELL BIOLOGY, 2003, 161 (02) :281-294
[10]   Histone H3 serine 10 phosphorylation by Aurora B causes HP1 dissociation from heterochromatin [J].
Hirota, T ;
Lipp, JJ ;
Toh, BH ;
Peters, JM .
NATURE, 2005, 438 (7071) :1176-1180