Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry.
The role of BubR1 has been established mainly in mitosis as an essential mitotic checkpoint protein although it is expressed throughout the cell cycle. To explore a possible role of BubR1 in regulating the G(2) phase of cell cycle, we have employed siRNA-mediated hBubR1 knockdown in HeLa cells. Here, we demonstrate that reducing BubR1 levels during the G(2) phase causes accelerated mitotic entry. As expected, BubR1 depletion leads to degradation of cyclin B(1) in the G(2) phase. Intriguingly, cyclin B(1) is prematurely targeted to centrosomes appearing at early G(2) phase in BubR1-depleted cells despite its low levels. This is in contrast to control cells where cyclin B(1) appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G(2) is aberrantly high in BubR1-depleted cells. Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B(1) probably leading to premature mitotic entry. This study is the first to suggest a role of hBubR1 in controlling centrosome targeting of cyclin B(1) and timing of mitotic entry.
Department of Biochemistry, Ajou University School of Medicine, Suwon, Korea.
Sun-Yi
SY
Park
Sujeong
S
Kim
Hyeseon
H
Cho
Soon-Hwan
SH
Kwon
Sunyoung
S
Chae
Dongmin
D
Kang
Yeon-Sun
YS
Seong
Hyeseong
H
Cho
D016203:CDC2 Protein Kinase / Q000378:metabolism; D045744:Cell Line, Tumor; D018385:Centrosome / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D016195:G2 Phase; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D034741:RNA, Small Interfering / Q000378:metabolism
C534699:CCNB1 protein, human; D002868:Chromosomal Proteins, Non-Histone; D019926:Cyclin B; D056744:Cyclin B1; D008840:Microfilament Proteins; D034741:RNA, Small Interfering; C094772:centromere protein F; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase