Mitotic phosphorylation of histone H3 threonine 80

被引:28
作者
Hammond, Sharra L. [1 ,2 ]
Byrum, Stephanie D. [3 ]
Namjoshi, Sarita [1 ]
Graves, Hillary K. [1 ]
Dennehey, Briana K. [1 ]
Tackett, Alan J. [3 ]
Tyler, Jessica K. [1 ,2 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA
[2] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA
[3] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA
关键词
histone phosphorylation; mitosis; chromatin condensation; MITOSIS-SPECIFIC PHOSPHORYLATION; NUCLEOSOME CORE PARTICLE; AURORA-B; CHROMOSOME CONDENSATION; KINASE; IDENTIFICATION; METHYLATION; COMPLEXES; PROTEINS; SPINDLE;
D O I
10.4161/cc.27269
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The onset and regulation of mitosis is dependent on phosphorylation of a wide array of proteins. Among the proteins that are phosphorylated during mitosis is histone H3, which is heavily phosphorylated on its N-terminal tail. In addition, large-scale mass spectrometry screens have revealed that histone H3 phosphorylation can occur at multiple sites within its globular domain, yet detailed analyses of the functions of these phosphorylations are lacking. Here, we explore one such histone H3 phosphorylation site, threonine 80 (H3T80), which is located on the nucleosome surface. Phosphorylated H3T80 (H3T80ph) is enriched in metazoan cells undergoing mitosis. Unlike H3S10 and H3S28, H3T80 is not phosphorylated by the Aurora B kinase. Further, mutations of T80 to either glutamic acid, a phosphomimetic, or to alanine, an unmodifiable residue, result in an increase in cells in prophase and an increase in anaphase/telophase bridges, respectively. SILAC-coupled mass spectrometry shows that phosphorylated H3T80 (H3T80ph) preferentially interacts with histones H2A and H4 relative to non-phosphorylated H3T80, and this result is supported by increased binding of H3T80ph to histone octamers in vitro. These findings support a model where H3T80ph, protruding from the nucleosome surface, promotes interactions between adjacent nucleosomes to promote chromatin compaction during mitosis in metazoan cells.
引用
收藏
页码:440 / 452
页数:13
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