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The kinase haspin is required for mitotic histone H3 Thr 3 phosphorylation and normal metaphase chromosome alignment

阿平添加于 2009-5-24 21:40 | 2586 次阅读 | 0 个评论

作者
Dai J, Sultan S, Taylor SS, Higgins JMG
摘要
Post-translational modifications of conserved N-terminal tail residues in histones regulate many aspects of chromosome activity. Thr 3 of histone H3 is highly conserved, but the significance of its phosphorylation is unclear, and the identity of the corresponding kinase unknown. Immunostaining with phospho-specific antibodies in mammalian cells reveals mitotic phosphorylation of H3 Thr 3 in prophase and its dephosphorylation during anaphase. Furthermore we find that haspin, a member of a distinctive group of protein kinases present in diverse eukaryotes, phosphorylates H3 at Thr 3 in vitro. Importantly, depletion of haspin by RNA interference reveals that this kinase is required for H3 Thr 3 phosphorylation in mitotic cells. In addition to its chromosomal association, haspin is found at the centrosomes and spindle during mitosis. Haspin RNA interference causes misalignment of metaphase chromosomes, and overexpression delays progression through early mitosis. This work reveals a new kinase involved in composing the histone code and adds haspin to the select group of kinases that integrate regulation of chromosome and spindle function during mitosis and meiosis.
详细资料
- 关键词: Amino Acid Sequence; *Chromosomes, Human; Hela Cells; Histones/chemistry/*metabolism; Humans; Intracellular Signaling Peptides and Proteins; *Metaphase; Microscopy, Electron; Mitosis/*physiology; Molecular Sequence Data; Phosphorylation; Protein-Serine-Threonine Kinases/chemistry/metabolism/*physiology; Recombinant Proteins/metabolism; Subcellular Fractions/metabolism; Threonine/*metabolism
- 文献种类: Journal Article
- 期刊名称: Genes & Development
- 期刊缩写: Genes Dev
- 期卷页: 2005年第19卷第4期 472-488页
- 地址: Division of Rheumatology, Immunology and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
- ISBN: 0890-9369
- 备注:PMID:15681610
学科领域生物医药 » 生物学
标签

Haspin H3T3
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