HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors
| Autor: | Kazuhiko S.K. Uchida, Jennifer G. DeLuca, Kosuke Sako, Youko Hirayama, Abe Yusuke, Kentaro Takagaki, Toru Hirota, Jacob A. Herman |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chromosomal Proteins Non-Histone Carcinogenesis Centromere Biorientation Aurora B kinase Mitosis Cell Cycle Proteins Spindle Apparatus macromolecular substances Biology Microtubules Article General Biochemistry Genetics and Molecular Biology Chromosome segregation 03 medical and health sciences 0302 clinical medicine Microtubule Cell Line Tumor Chromosomal Instability Chromosome Segregation Aurora Kinase B Humans Kinetochores Molecular Biology Kinetochore technology industry and agriculture Cell Biology Cell biology Spindle apparatus Spindle checkpoint 030104 developmental biology Chromobox Protein Homolog 5 embryonic structures Heterochromatin protein 1 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Developmental Cell. 36:487-497 |
| ISSN: | 1534-5807 |
| Popis: | Incorrect attachment of kinetochore microtubules is the leading cause of chromosome missegregation in cancers. The highly conserved chromosomal passenger complex (CPC), containing mitotic kinase Aurora B as a catalytic subunit, ensures faithful chromosome segregation through destabilizing incorrect microtubule attachments and promoting bi-orientation of chromosomes on the mitotic spindle. It is unknown whether CPC dysfunction affects chromosome segregation fidelity in cancers and, if so, how. Here we show that heterochromatin protein 1 (HP1) is an essential CPC component required for full Aurora B activity. HP1 binding to the CPC becomes particularly important when Aurora B phosphorylates kinetochore targets to eliminate erroneous microtubule-attachments. Remarkably, a reduced proportion of HP1-bound to CPC is widespread in cancers, which causes an impairment in Aurora B activity. These results indicate that HP1 is an essential modulator for CPC function, and identify a molecular basis for chromosome segregation errors in cancer cells. |
| Databáze: | OpenAIRE |
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