scholarly journals Survivin dynamics increases at centromeres during G2/M phase transition and is regulated by microtubule-attachment and Aurora B kinase activity

2004 ◽  
Vol 117 (18) ◽  
pp. 4033-4042 ◽  
Author(s):  
V. A. Beardmore
Keyword(s):  
Phase Transition ◽  
Kinase Activity ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Microtubule Attachment ◽  
M Phase

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 Cdc7 kinase stimulates Aurora B kinase in M-phase

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sayuri Ito ◽  
Hidemasa Goto ◽  
Kinue Kuniyasu ◽  
Mayumi Shindo ◽  
Masayuki Yamada ◽  
...  
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Kinase Activity ◽  
Phosphorylation Site ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Mitotic Kinase ◽  
M Phase ◽  
Phase Progression ◽  
Autophosphorylation Site

AbstractThe conserved serine-threonine kinase, Cdc7, plays a crucial role in initiation of DNA replication by facilitating the assembly of an initiation complex. Cdc7 is expressed at a high level and exhibits significant kinase activity not only during S-phase but also during G2/M-phases. A conserved mitotic kinase, Aurora B, is activated during M-phase by association with INCENP, forming the chromosome passenger complex with Borealin and Survivin. We show that Cdc7 phosphorylates and stimulates Aurora B kinase activity in vitro. We identified threonine-236 as a critical phosphorylation site on Aurora B that could be a target of Cdc7 or could be an autophosphorylation site stimulated by Cdc7-mediated phosphorylation elsewhere. We found that threonines at both 232 (that has been identified as an autophosphorylation site) and 236 are essential for the kinase activity of Aurora B. Cdc7 down regulation or inhibition reduced Aurora B activity in vivo and led to retarded M-phase progression. SAC imposed by paclitaxel was dramatically reversed by Cdc7 inhibition, similar to the effect of Aurora B inhibition under the similar situation. Our data show that Cdc7 contributes to M-phase progression and to spindle assembly checkpoint most likely through Aurora B activation.

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 Aurora B kinase and protein phosphatase 1 have opposing roles in modulating kinetochore assembly

2008 ◽  
Vol 181 (2) ◽  
pp. 241-254 ◽  
Author(s):  
Michael J. Emanuele ◽  
Weijie Lan ◽  
Miri Jwa ◽  
Stephanie A. Miller ◽  
Clarence S.M. Chan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Protein Phosphatase 1 ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Culture Cells ◽  
Kinetochore Assembly ◽  
M Phase ◽  
Egg Extracts ◽  
Cycle Dependent

The outer kinetochore binds microtubules to control chromosome movement. Outer kinetochore assembly is restricted to mitosis, whereas the inner kinetochore remains tethered to centromeres throughout the cell cycle. The cues that regulate this transient assembly are unknown. We find that inhibition of Aurora B kinase significantly reduces outer kinetochore assembly in Xenopus laevis and human tissue culture cells, frog egg extracts, and budding yeast. In X. leavis M phase extracts, preassembled kinetochores disassemble after inhibiting Aurora B activity with either drugs or antibodies. Kinetochore disassembly, induced by Aurora B inhibition, is rescued by restraining protein phosphatase 1 (PP1) activity. PP1 is necessary for kinetochores to disassemble at the exit from M phase, and purified enzyme is sufficient to cause disassembly on isolated mitotic nuclei. These data demonstrate that Aurora B activity is required for kinetochore maintenance and that PP1 is necessary and sufficient to disassemble kinetochores. We suggest that Aurora B and PP1 coordinate cell cycle–dependent changes in kinetochore assembly though phosphorylation of kinetochore substrates.

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 The Ndc80 complex bridges two Dam1 complex rings

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jae ook Kim ◽  
Alex Zelter ◽  
Neil T Umbreit ◽  
Athena Bollozos ◽  
Michael Riffle ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Aurora B ◽  
Aurora B Kinase ◽  
Microtubule Attachment ◽  
Sister Chromatids ◽  
Ndc80 Complex ◽  
Interaction Regions ◽  
Dam1 Complex

Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital.

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
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