MTBP plays a crucial role in mitotic progression and chromosome segregation

N. Agarwal, Y. Tochigi, A. S. Adhikari, S. Cui, Yan Cui, T. Iwakuma

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Murine double minute 2 (MDM2) binding protein (MTBP) has been implicated in tumor cell proliferation, but the underlying mechanisms remain unclear. The results of MTBP expression analysis during cell cycle progression demonstrated that MTBP protein was rapidly degraded during mitosis. Immunofluorescence studies revealed that a portion of MTBP was localized at the kinetochores during prometaphase. MTBP overexpression delayed mitotic progression from nuclear envelope breakdown (NEB) to anaphase onset and induced abnormal chromosome segregation such as lagging chromosomes, chromosome bridges, and multipolar chromosome segregation. Conversely, MTBP downmodulation caused an abbreviated metaphase and insufficient mitotic arrest, resulting in abnormal chromosome segregation, aneuploidy, decreased cell proliferation, senescence, and cell death, similar to that of Mad2 (mitotic arrest-deficient 2) downmodulation. Furthermore, MTBP downmodulation inhibited the accumulation of Mad1 and Mad2, but not BubR1 (budding uninhibited by benzimidazoles related 1), on the kinetochores, whereas MTBP overexpression inhibited the release of Mad2 from the metaphase kinetochores. These results may imply that MTBP has an important role in recruiting and/or retaining the Mad1/Mad2 complex at the kinetochores during prometaphase, but its degradation is required for silencing the mitotic checkpoint. Together, this study indicates that MTBP has a crucial role in proper mitotic progression and faithful chromosome segregation, providing new insights into regulation of the mitotic checkpoint.

Original languageEnglish (US)
Pages (from-to)1208-1219
Number of pages12
JournalCell Death and Differentiation
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2011
Externally publishedYes

Fingerprint

Kinetochores
Chromosome Segregation
Prometaphase
M Phase Cell Cycle Checkpoints
Metaphase
Proto-Oncogene Proteins c-mdm2
Chromosomes
Cell Proliferation
Benzimidazoles
Anaphase
Cell Aging
Nuclear Envelope
Aneuploidy
Mitosis
Fluorescent Antibody Technique
Cell Cycle
Carrier Proteins
Cell Death
Neoplasms
Proteins

Keywords

  • MDM2
  • MTBP
  • checkpoint
  • chromosome segregation
  • mitosis

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

MTBP plays a crucial role in mitotic progression and chromosome segregation. / Agarwal, N.; Tochigi, Y.; Adhikari, A. S.; Cui, S.; Cui, Yan; Iwakuma, T.

In: Cell Death and Differentiation, Vol. 18, No. 7, 01.07.2011, p. 1208-1219.

Research output: Contribution to journalArticle

Agarwal, N, Tochigi, Y, Adhikari, AS, Cui, S, Cui, Y & Iwakuma, T 2011, 'MTBP plays a crucial role in mitotic progression and chromosome segregation', Cell Death and Differentiation, vol. 18, no. 7, pp. 1208-1219. https://doi.org/10.1038/cdd.2010.189
Agarwal, N. ; Tochigi, Y. ; Adhikari, A. S. ; Cui, S. ; Cui, Yan ; Iwakuma, T. / MTBP plays a crucial role in mitotic progression and chromosome segregation. In: Cell Death and Differentiation. 2011 ; Vol. 18, No. 7. pp. 1208-1219.
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