論文 - 詳細
| RRC ID | 54485 |
|---|---|
| 著者 | Shimada M, Goshima T, Matsuo H, Johmura Y, Haruta M, Murata K, Tanaka H, Ikawa M, Nakanishi K, Nakanishi M. |
| タイトル | Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis. |
| ジャーナル | Nat Commun |
| Abstract |
Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation. |
| 巻・号 | 7 |
| ページ | 12059 |
| 公開日 | 2016-7-8 |
| DOI | 10.1038/ncomms12059 |
| PII | ncomms12059 |
| PMID | 27389782 |
| PMC | PMC4941122 |
| MeSH | Animals Aurora Kinase B / genetics* Aurora Kinase B / metabolism Cell Line Chromosome Segregation* Fibroblasts / cytology Fibroblasts / metabolism HeLa Cells Histones / antagonists & inhibitors Histones / genetics* Histones / metabolism Humans Intracellular Signaling Peptides and Proteins / antagonists & inhibitors Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Kinetochores / metabolism Kinetochores / ultrastructure Mice Mice, Knockout Mitosis* Phosphorylation Protein Serine-Threonine Kinases / antagonists & inhibitors Protein Serine-Threonine Kinases / genetics Protein Serine-Threonine Kinases / metabolism RNA, Small Interfering / genetics RNA, Small Interfering / metabolism Serine / metabolism* Spindle Apparatus / metabolism Spindle Apparatus / ultrastructure |
| IF | 11.878 |
| 引用数 | 14 |
| リソース情報 | |
| 遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB04385) |