scholarly journals Gradient of Increasing Aurora B Kinase Activity Is Required for Cells to Execute Mitosis

2010 ◽  
Vol 285 (51) ◽  
pp. 40163-40170 ◽  
Author(s):  
Zhenjie Xu ◽  
Paola Vagnarelli ◽  
Hiromi Ogawa ◽  
Kumiko Samejima ◽  
William C. Earnshaw
Keyword(s):  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase

scholarly journals Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere

2019 ◽  
Vol 218 (10) ◽  
pp. 3223-3236 ◽  
Author(s):  
Yuichiro Asai ◽  
Koh Fukuchi ◽  
Yuji Tanno ◽  
Saki Koitabashi-Kiyozuka ◽  
Tatsuyuki Kiyozuka ◽  
...  
Keyword(s):  
Chromosome Segregation ◽  
Chromosomal Instability ◽  
Kinase Activity ◽  
Fine Tuning ◽  
Aurora B ◽  
The Novel ◽  
Aurora B Kinase ◽  
Microtubule Attachment ◽  
Molecular Events

The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation at the kinetochore. Here, we show that localization of SET/TAF1, an oncogene product, to centromeres maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore–microtubule attachment. SET localizes at the inner centromere by interacting directly with shugoshin 2, with SET levels declining at increased distances between kinetochore pairs, leading to establishment of chromosome bi-orientation. Moreover, SET overexpression induces chromosomal instability by disrupting kinetochore–microtubule attachment. Thus, our findings reveal the novel role of SET in fine-tuning the phosphorylation level at the kinetochore by balancing the activities of Aurora B and PP2A.

scholarly journals VX-680 Inhibits Aurora A and Aurora B Kinase Activity in Human Cells

Cell Cycle ◽  
2007 ◽  
Vol 6 (22) ◽  
pp. 2846-2854 ◽  
Author(s):  
Rebecca K. Tyler ◽  
Natalia Shpiro ◽  
Rodolfo Marquez ◽  
Patrick A. Eyers
Keyword(s):  
Kinase Activity ◽  
Human Cells ◽  
Aurora B ◽  
Aurora A ◽  
Aurora B Kinase

The dietary flavonoid luteolin inhibits Aurora B kinase activity and blocks proliferation of cancer cells

2012 ◽  
Vol 46 (5) ◽  
pp. 388-396 ◽  
Author(s):  
Fang Xie ◽  
Qingyu Lang ◽  
Mei Zhou ◽  
Haoxing Zhang ◽  
Zhishun Zhang ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Dietary Flavonoid

scholarly journals Use of DT40 conditional-knockout cell lines to study chromosomal passenger protein function

2010 ◽  
Vol 38 (6) ◽  
pp. 1655-1659 ◽  
Author(s):  
Xavier Fant ◽  
Kumiko Samejima ◽  
Ana Carvalho ◽  
Hiromi Ogawa ◽  
Zhenjie Xu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Protein Function ◽  
Kinase Activity ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger ◽  
Passenger Protein

The CPC [chromosomal passenger complex; INCENP (inner centromere protein), Aurora B kinase, survivin and borealin] is implicated in many mitotic processes. In the present paper we describe how we generated DT40 conditional-knockout cell lines for incenp1 and survivin1 to better understand the role of these CPC subunits in the control of Aurora B kinase activity. These lines enabled us to reassess current knowledge of survivin function and to show that INCENP acts as a rheostat for Aurora B activity.

scholarly journals Bub1 overexpression induces aneuploidy and tumor formation through Aurora B kinase hyperactivation

2011 ◽  
Vol 193 (6) ◽  
pp. 1049-1064 ◽  
Author(s):  
Robin M. Ricke ◽  
Karthik B. Jeganathan ◽  
Jan M. van Deursen
Keyword(s):  
Protein Kinase ◽  
Transgenic Mice ◽  
Chromosome Segregation ◽  
Kinase Activity ◽  
Tumor Formation ◽  
High Expression ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Clinical Prognosis ◽  
Poor Clinical Prognosis

High expression of the protein kinase Bub1 has been observed in a variety of human tumors and often correlates with poor clinical prognosis, but its molecular and cellular consequences and role in tumorigenesis are unknown. Here, we demonstrate that overexpression of Bub1 in mice leads to near-diploid aneuploidies and tumor formation. We found that chromosome misalignment and lagging are the primary mitotic errors responsible for the observed aneuploidization. High Bub1 levels resulted in aberrant Bub1 kinase activity and hyperactivation of Aurora B kinase. When Aurora B activity is suppressed, pharmacologically or via BubR1 overexpression, chromosome segregation errors caused by Bub1 overexpression are largely corrected. Importantly, Bub1 transgenic mice overexpressing Bub1 developed various kinds of spontaneous tumors and showed accelerated Myc-induced lymphomagenesis. Our results establish that Bub1 has oncogenic properties and suggest that Aurora B is a critical target through which overexpressed Bub1 drives aneuploidization and tumorigenesis.

scholarly journals Aurora B kinase is recruited to multiple discrete kinetochore and centromere regions in human cells

2020 ◽  
Vol 219 (3) ◽  
Author(s):  
Amanda J. Broad ◽  
Keith F. DeLuca ◽  
Jennifer G. DeLuca
Keyword(s):  
Kinase Activity ◽  
Critical Role ◽  
Aurora B ◽  
Histone H2a ◽  
Aurora B Kinase ◽  
Spindle Microtubules ◽  
Kinetochore Region ◽  
20 Nm ◽  
Discrete Populations ◽  
Early Mitosis

Aurora B kinase has a critical role in regulating attachments between kinetochores and spindle microtubules during mitosis. Early in mitosis, kinase activity at kinetochores is high to promote attachment turnover, and in later mitosis, activity decreases to ensure attachment stabilization. Aurora B localizes prominently to inner centromeres, and a population of the kinase is also detected at kinetochores. How Aurora B is recruited to and evicted from these regions to regulate kinetochore-microtubule attachments remains unclear. Here, we identified and investigated discrete populations of Aurora B at the centromere/kinetochore region. An inner centromere pool is recruited by Haspin phosphorylation of histone H3, and a kinetochore-proximal outer centromere pool is recruited by Bub1 phosphorylation of histone H2A. Finally, a third pool resides ~20 nm outside of the inner kinetochore protein CENP-C in early mitosis and does not require either the Bub1/pH2A/Sgo1 or Haspin/pH3 pathway for localization or activity. Our results suggest that distinct molecular pathways are responsible for Aurora B recruitment to centromeres and kinetochores.

scholarly journals CSC-1

2003 ◽  
Vol 161 (2) ◽  
pp. 229-236 ◽  
Author(s):  
Alper Romano ◽  
Annika Guse ◽  
Ivica Krascenicova ◽  
Heinke Schnabel ◽  
Ralf Schnabel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Genetic Analysis ◽  
Chromosome Segregation ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
C Elegans ◽  
The Individual

The Aurora B kinase complex is a critical regulator of chromosome segregation and cytokinesis. In Caenorhabditis elegans, AIR-2 (Aurora B) function requires ICP-1 (Incenp) and BIR-1 (Survivin). In various systems, Aurora B binds to orthologues of these proteins. Through genetic analysis, we have identified a new subunit of the Aurora B kinase complex, CSC-1. C. elegans embryos depleted of CSC-1, AIR-2, ICP-1, or BIR-1 have identical phenotypes. CSC-1, BIR-1, and ICP-1 are interdependent for their localization, and all are required for AIR-2 localization. In vitro, CSC-1 binds directly to BIR-1. The CSC-1/BIR-1 complex, but not the individual subunits, associates with ICP-1. CSC-1 associates with ICP-1, BIR-1, and AIR-2 in vivo. ICP-1 dramatically stimulates AIR-2 kinase activity. This activity is not stimulated by CSC-1/BIR-1, suggesting that these two subunits function as targeting subunits for AIR-2 kinase.

scholarly journals Phosphorylation at serine 331 is required for Aurora B activation

2011 ◽  
Vol 195 (3) ◽  
pp. 449-466 ◽  
Author(s):  
Eleni Petsalaki ◽  
Tonia Akoumianaki ◽  
Elizabeth J. Black ◽  
David A.F. Gillespie ◽  
George Zachos
Keyword(s):  
Cell Division ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Chromosomal Passenger Complex ◽  
Chromosome Missegregation ◽  
Mitotic Delay ◽  
Chromosomal Passenger ◽  
Spontaneous Chromosome ◽  
Chk1 Kinase

Aurora B kinase activity is required for successful cell division. In this paper, we show that Aurora B is phosphorylated at serine 331 (Ser331) during mitosis and that phosphorylated Aurora B localizes to kinetochores in prometaphase cells. Chk1 kinase is essential for Ser331 phosphorylation during unperturbed prometaphase or during spindle disruption by taxol but not nocodazole. Phosphorylation at Ser331 is required for optimal phosphorylation of INCENP at TSS residues, for Survivin association with the chromosomal passenger complex, and for complete Aurora B activation, but it is dispensable for Aurora B localization to centromeres, for autophosphorylation at threonine 232, and for association with INCENP. Overexpression of Aurora BS331A, in which Ser331 is mutated to alanine, results in spontaneous chromosome missegregation, cell multinucleation, unstable binding of BubR1 to kinetochores, and impaired mitotic delay in the presence of taxol. We propose that Chk1 phosphorylates Aurora B at Ser331 to fully induce Aurora B kinase activity. These results indicate that phosphorylation at Ser331 is an essential mechanism for Aurora B activation.

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