Depletion of BubR1 promotes premature centrosomal localization of cyclin B1 and accelerates mitotic entry

Sun Yi Park, Sujeong Kim, Hyeseon Cho, Soon Hwan Kwon, Sunyoung Chae, Dongmin Kang, Yeon Sun Seong, Hyeseong Cho

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

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 G2 phase of cell cycle, we have employed siRNA-mediated hBubR1 knockdown in HeLa cells. Here, we demonstrate that reducing BubR1 levels during the G2 phase causes accelerated mitotic entry. As expected, BubR1 depletion leads to degradation of cyclin B1 in the G2 phase. Intriguingly, cyclin B1 is prematurely targeted to centrosomes appearing at early G2 phase in BubR1-depleted cells despite its low levels. This is in contrast to control cells where cyclin B1 appears at the centrosomes in early prophase based on cell cycle-specific localization of CENP-F. Furthermore, cyclin B/Cdk1 kinase activity in early G2 is aberrantly high in BubR1-depleted cells. Together, our results indicate that hBubR1 depletion triggers premature centrosomal localization of cyclin B1 probably leading to premature mitotic entry. This study is the first to suggest a role of hBubR1 in controlling centrosome targeting of cyclin B1 and timing of mitotic entry.

Original languageEnglish
Pages (from-to)1754-1764
Number of pages11
JournalCell Cycle
Volume8
Issue number11
DOIs
StatePublished - 1 Jun 2009

Bibliographical note

Funding Information:
This study was supported by grants from the National R&D Program for Cancer Control, Ministry of Health and Welfare (0820060) and from Korea Science and Engineering Foundation through Chronic Inflammatory Disease Research Center (R13-2003-019), Republic of Korea.

Keywords

  • BubR1
  • CENP-F
  • Centrosomes
  • Cyclin B
  • G/M transition

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