Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation

Robin M. Ricke, Jan Van Deursen

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

High expression of the mitotic kinase Bub1 is associated with a variety of human cancers and correlates with poor clinical prognosis, but whether Bub1 alone can drive tumorigenesis was unknown. We provided conclusive evidence that Bub1 has oncogenic properties by generating transgenic mice that overexpress Bub1 in a wide variety of tissues, resulting in aneuploidization. Consistently, Bub1 transgenic mice developed various kinds of spontaneous tumors as well as accelerated Mycinduced lymphomagenesis. While the mitotic checkpoint was robust in Bub1 overexpressing cells, misaligned and lagging chromosomes were observed. These defects originated from increased Aurora B activity and could be suppressed by inhibition of Aurora B. Taken together, this indicates that Bub1 has oncogenic properties and imply that aneuploidization and tumorigenesis result from Aurora B-dependent missegregation. Here, we focus on the complex relationship between Bub1 and Aurora B and discuss the broader implications of Bub1- dependent Aurora B activation in mediating error correction.

Original languageEnglish (US)
Pages (from-to)3645-3651
Number of pages7
JournalCell Cycle
Volume10
Issue number21
DOIs
StatePublished - Nov 1 2011

Fingerprint

Transgenic Mice
Carcinogenesis
Chromosomes
M Phase Cell Cycle Checkpoints
Neoplasms
Phosphotransferases

Keywords

  • Aneuploidy
  • Aurora B
  • Bub1
  • Chromosome segregation
  • Mitotic checkpoint

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation. / Ricke, Robin M.; Van Deursen, Jan.

In: Cell Cycle, Vol. 10, No. 21, 01.11.2011, p. 3645-3651.

Research output: Contribution to journalArticle

@article{6b4c06492d284d80a4f901fbc6a5b614,
title = "Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation",
abstract = "High expression of the mitotic kinase Bub1 is associated with a variety of human cancers and correlates with poor clinical prognosis, but whether Bub1 alone can drive tumorigenesis was unknown. We provided conclusive evidence that Bub1 has oncogenic properties by generating transgenic mice that overexpress Bub1 in a wide variety of tissues, resulting in aneuploidization. Consistently, Bub1 transgenic mice developed various kinds of spontaneous tumors as well as accelerated Mycinduced lymphomagenesis. While the mitotic checkpoint was robust in Bub1 overexpressing cells, misaligned and lagging chromosomes were observed. These defects originated from increased Aurora B activity and could be suppressed by inhibition of Aurora B. Taken together, this indicates that Bub1 has oncogenic properties and imply that aneuploidization and tumorigenesis result from Aurora B-dependent missegregation. Here, we focus on the complex relationship between Bub1 and Aurora B and discuss the broader implications of Bub1- dependent Aurora B activation in mediating error correction.",
keywords = "Aneuploidy, Aurora B, Bub1, Chromosome segregation, Mitotic checkpoint",
author = "Ricke, {Robin M.} and {Van Deursen}, Jan",
year = "2011",
month = "11",
day = "1",
doi = "10.4161/cc.10.21.18156",
language = "English (US)",
volume = "10",
pages = "3645--3651",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "21",

}

TY - JOUR

T1 - Aurora B hyperactivation by Bub1 overexpression promotes chromosome missegregation

AU - Ricke, Robin M.

AU - Van Deursen, Jan

PY - 2011/11/1

Y1 - 2011/11/1

N2 - High expression of the mitotic kinase Bub1 is associated with a variety of human cancers and correlates with poor clinical prognosis, but whether Bub1 alone can drive tumorigenesis was unknown. We provided conclusive evidence that Bub1 has oncogenic properties by generating transgenic mice that overexpress Bub1 in a wide variety of tissues, resulting in aneuploidization. Consistently, Bub1 transgenic mice developed various kinds of spontaneous tumors as well as accelerated Mycinduced lymphomagenesis. While the mitotic checkpoint was robust in Bub1 overexpressing cells, misaligned and lagging chromosomes were observed. These defects originated from increased Aurora B activity and could be suppressed by inhibition of Aurora B. Taken together, this indicates that Bub1 has oncogenic properties and imply that aneuploidization and tumorigenesis result from Aurora B-dependent missegregation. Here, we focus on the complex relationship between Bub1 and Aurora B and discuss the broader implications of Bub1- dependent Aurora B activation in mediating error correction.

AB - High expression of the mitotic kinase Bub1 is associated with a variety of human cancers and correlates with poor clinical prognosis, but whether Bub1 alone can drive tumorigenesis was unknown. We provided conclusive evidence that Bub1 has oncogenic properties by generating transgenic mice that overexpress Bub1 in a wide variety of tissues, resulting in aneuploidization. Consistently, Bub1 transgenic mice developed various kinds of spontaneous tumors as well as accelerated Mycinduced lymphomagenesis. While the mitotic checkpoint was robust in Bub1 overexpressing cells, misaligned and lagging chromosomes were observed. These defects originated from increased Aurora B activity and could be suppressed by inhibition of Aurora B. Taken together, this indicates that Bub1 has oncogenic properties and imply that aneuploidization and tumorigenesis result from Aurora B-dependent missegregation. Here, we focus on the complex relationship between Bub1 and Aurora B and discuss the broader implications of Bub1- dependent Aurora B activation in mediating error correction.

KW - Aneuploidy

KW - Aurora B

KW - Bub1

KW - Chromosome segregation

KW - Mitotic checkpoint

UR - http://www.scopus.com/inward/record.url?scp=80655123645&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80655123645&partnerID=8YFLogxK

U2 - 10.4161/cc.10.21.18156

DO - 10.4161/cc.10.21.18156

M3 - Article

VL - 10

SP - 3645

EP - 3651

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 21

ER -