title: HP1-Assisted Aurora B Kinase Activity Prevents Chromosome Segregation Errors.
abstract: 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 biorientation 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.
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Sako
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Takagaki
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Hirayama
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan.
authors.forename: Kazuhiko S K
authors.initials: KS
authors.lastname: Uchida
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Jacob A
authors.initials: JA
authors.lastname: Herman
authors.affiliation: Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523, USA.
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: DeLuca
authors.affiliation: Division of Experimental Pathology, Cancer Institute of the Japanese Foundation for Cancer Research (JFCR), Tokyo 135-8550, Japan. Electronic address: thirota@jfcr.or.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Hirota
mesh_terms: D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics*; D006801:Humans; D018386:Kinetochores / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D000090266:Chromobox Protein Homolog 5; D064107:Aurora Kinase B