title: Dual roles of human BubR1, a mitotic checkpoint kinase, in the monitoring of chromosomal instability.
abstract: In this study, we show that the formation of polyploidy following sustained mitotic checkpoint activation appears to be preceded by the ubiquitin-dependent proteolysis of hBubR1. In addition, the level of hBubR1 is significantly reduced not only in polyploid cells created by sustained mitotic spindle damage, but also in 21 (31.3%) of 67 human colon adenocarcinomas tested. Importantly, the introduction of hBubR1 triggers the apoptosis of polyploid cells formed by aberrant exit from mitosis and inhibits the growth of tumors established with these cells in athymic nude mice. These results suggest that hBubR1-mediated apoptosis prevents the propagation of cells that breach the mitotic checkpoint and that the control of hBubR1 protein level is an important factor in the acquisition of preneoplastic polyploidy.
authors.affiliation: Research Institute, National Cancer Center, Goyang, Gyeonggi, 411-764, Korea.
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Shin
authors.forename: Kwan Hyuck
authors.initials: KH
authors.lastname: Baek
authors.forename: Ae Hwa
authors.initials: AH
authors.lastname: Jeon
authors.forename: Moon Taek
authors.initials: MT
authors.lastname: Park
authors.forename: Su Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Chang Mo
authors.initials: CM
authors.lastname: Kang
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Lee
authors.forename: Seong Ho
authors.initials: SH
authors.lastname: Yoo
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Sung
authors.forename: Frank
authors.initials: F
authors.lastname: McKeon
authors.forename: Chang Woo
authors.initials: CW
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D018797:Cell Cycle Proteins; D043171:Chromosomal Instability / Q000235:genetics*; D003001:Cloning, Molecular; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008938:Mitosis / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D010766:Phosphorylation; D011123:Polyploidy; D011489:Protein Denaturation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D008941:Spindle Apparatus; D014183:Transplantation, Heterologous / Q000473:pathology; D025801:Ubiquitin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C584278:Bub1b protein, mouse; D018797:Cell Cycle Proteins; D025801:Ubiquitin; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D020169:Caspases; D015739:Nocodazole