Haspin - A mitotic histone kinase required for metaphase chromosome alignment

被引:58
作者
Dai, J [1 ]
Higgins, JMG [1 ]
机构
[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA
关键词
haspin; Gsg2; mitosis; centromere; histone phosphorylation; serine/threonine kinase; chromatin; aurora B; chromosome segregation;
D O I
10.4161/cc.4.5.1683
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The fidelity of chromosome segregation during cell division is critical to maintain genomic stability and to prevent cancer and birth defects. A key set of kinases that regulates this process has been identified and characterized over the last few years, including the Aurora, Polo and Nek families. Recently we proposed that a little-studied kinase known as haspin is a new member of this important group. During mitosis haspin is phosphorylated, associates with the chromosomes, centrosomes and spindle, and is responsible for phosphorylation of histone H3 at threonine-3. Depletion of haspin using RNA interference prevents normal alignment of chromosomes at metaphase, suggesting that haspin plays a crucial role in chromosome segregation. Here we discuss possible mechanisms of haspin action and the function of histone phosphorylation in mitosis. We also outline some of the questions raised by these new findings and consider what role haspin might play in cancer.
引用
收藏
页码:665 / 668
页数:4
相关论文
共 49 条
[21]   OVCA1: emerging as a bona fide tumor suppressor [J].
Jensen, MR ;
Helin, K .
GENES & DEVELOPMENT, 2004, 18 (03) :245-248
[22]   Translating the histone code [J].
Jenuwein, T ;
Allis, CD .
SCIENCE, 2001, 293 (5532) :1074-1080
[23]   Aurora-kinase inhibitors as anticancer agents [J].
Keen, N ;
Taylor, S .
NATURE REVIEWS CANCER, 2004, 4 (12) :927-936
[24]   CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B inner centromeres and for kinetochore function [J].
Kunitoku, N ;
Sasayama, T ;
Marumoto, T ;
Zhang, DW ;
Honda, S ;
Kobayashi, O ;
Hatakeyama, K ;
Ushio, Y ;
Saya, H ;
Hirota, T .
DEVELOPMENTAL CELL, 2003, 5 (06) :853-864
[25]   The many faces of histone lysine methylation [J].
Lachner, M ;
Jenuwein, T .
CURRENT OPINION IN CELL BIOLOGY, 2002, 14 (03) :286-298
[26]   Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14 [J].
Lo, WS ;
Trievel, RC ;
Rojas, JR ;
Duggan, L ;
Hsu, JY ;
Allis, CD ;
Marmorstein, R ;
Berger, SL .
MOLECULAR CELL, 2000, 5 (06) :917-926
[27]   Cohesin release is required for sister chromatid resolution, but not for condensin-mediated compaction, at the onset of mitosis [J].
Losada, A ;
Hirano, M ;
Hirano, T .
GENES & DEVELOPMENT, 2002, 16 (23) :3004-3016
[28]   ''Holo''er than thou:: Chromosome segregation and kinetochore function in C-elegans [J].
Maddox, PS ;
Oegema, K ;
Desai, A ;
Cheeseman, IM .
CHROMOSOME RESEARCH, 2004, 12 (06) :641-653
[29]   Mitotic kinases as regulators of cell division and its checkpoints [J].
Nigg, EA .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2001, 2 (01) :21-32
[30]  
PAULSON JR, 1982, J BIOL CHEM, V257, P6064