The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis

Carmena, Mar; Wheelock, Michael; Funabiki, Hironori; Earnshaw, William C.

doi:10.1038/nrm3474

Cited by 794 publications

(939 citation statements)

References 253 publications

(355 reference statements)

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“…After regulating proper chromosome attachment at the inner centromeres, the CPC later moves to the spindle midzone to regulate microtubule dynamics (10)(11)(12)(13)(14). The CPC also localizes to the division site, where it participates in the control of cytokinesis by regulating furrow ingression and abscission (3). Additionally, Aurora B and INCENP play a pivotal role in the NoCut pathway, an evolutionarily conserved checkpoint that delays the completion of cytokinesis until all chromosomes have cleared the cleavage plane so as to avoid chromosome breakage during abscission (15)(16)(17).…”

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confidence: 99%

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Increased Aurora B activity causes continuous disruption of kinetochore–microtubule attachments and spindle instability

Muñoz-Barrera

Monje-Casas

2014

Proc. Natl. Acad. Sci. U.S.A.

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Aurora B kinase regulates the proper biorientation of sister chromatids during mitosis. Lack of Aurora B kinase function results in the inability to correct erroneous kinetochore-microtubule attachments and gives rise to aneuploidy. Interestingly, increased Aurora B activity also leads to problems with chromosome segregation, and overexpression of this kinase has been observed in various types of cancer. However, little is known about the mechanisms by which an increase in Aurora B kinase activity can impair mitotic progression and cell viability. Here, using a yeast model, we demonstrate that increased Aurora B activity as a result of the overexpression of the Aurora B and inner centromere protein homologs triggers defects in chromosome segregation by promoting the continuous disruption of chromosome-microtubule attachments even when sister chromatids are correctly bioriented. This disruption leads to a constitutive activation of the spindle-assembly checkpoint, which therefore causes a lack of cytokinesis even though spindle elongation and chromosome segregation take place. Finally, we demonstrate that this increase in Aurora B activity causes premature collapse of the mitotic spindle by promoting instability of the spindle midzone.

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“…Additionally, each kinetochore of every pair of sister chromatids must be connected to opposite spindle poles (biorientation or amphitelic attachment). Aurora B kinase plays a pivotal role in this process (3). After replication, sister chromatids are bound together by ringshaped cohesin complexes (4).…”

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confidence: 99%

Increased Aurora B activity causes continuous disruption of kinetochore–microtubule attachments and spindle instability

Muñoz-Barrera

Monje-Casas

2014

Proc. Natl. Acad. Sci. U.S.A.

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“…(15)(16)(17)(18)(19)(20)(21). The major kinase for these histone phosphorylation marks is Aurora B, which is part of the chromosomal passenger complex and plays essential roles in chromosome condensation, segregation, and cytokinesis during mitotic progression (22). Aurora B phosphorylates histones directly (17,21,(23)(24)(25)(26) or indirectly through activation of another kinase Haspin (27).…”

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confidence: 99%

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

Lin

Yuan

Han

et al. 2016

Journal of Biological Chemistry

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How histone post-translational modifications (PTMs) are inherited through the cell cycle remains poorly understood. Canonical histones are made in the S phase of the cell cycle. Combining mass spectrometry-based technologies and stable isotope labeling by amino acids in cell culture, we question the distribution of multiple histone PTMs on old versus new histones in synchronized human cells. We show that histone PTMs can be grouped into three categories according to their distributions. Most lysine mono-methylation and acetylation PTMs are either symmetrically distributed on old and new histones or are enriched on new histones. In contrast, most di-and tri-methylation PTMs are enriched on old histones, suggesting that the inheritance of different PTMs is regulated distinctly. Intriguingly, old and new histones are distinct in their phosphorylation status during early mitosis in the following three human cell types: HeLa, 293T, and human foreskin fibroblast cells. The mitotic hallmark H3S10ph is predominantly associated with old H3 at early mitosis and becomes symmetric with the progression of mitosis. This same distribution was observed with other mitotic phosphorylation marks, including H3T3/T6ph, H3.1/ 2S28ph, and H1.4S26ph but not S28/S31ph on the H3 variant H3.3. Although H3S10ph often associates with the neighboring Lys-9 di-or tri-methylations, they are not required for the asymmetric distribution of Ser-10 phosphorylation on the same H3 tail. Inhibition of the kinase Aurora B does not change the distribution despite significant reduction of H3S10ph levels. However, K9me2 abundance on the new H3 is significantly reduced after Aurora B inhibition, suggesting a cross-talk between H3S10ph and H3K9me2.In eukaryotes, histone proteins facilitate the packaging of DNA molecules. The DNA double helix wraps around histone octamers to form nucleosomes. A histone octamer contains two copies of each core histone H3, H4, H2A, and H2B. A 5th histone, histone H1, is associated with the linker DNA which lies between the nucleosomes. Canonical histone proteins are cell cycle-dependent and are produced in S phase (1, 2), whereas cell cycle-independent histone variants (e.g. H3.3) are synthesized throughout the cell cycle (3). Histone proteins carry numerous post-translational modifications (PTMs) 3 that are involved in multiple functions such as epigenetic regulation of transcription, DNA damage repair, and cell cycle progression (4, 5). To maintain lineage identity and to guide proper transcription, cells must replicate PTMs from old histones onto new histones at each cell division. Major efforts have been devoted to understanding how histones themselves are transmitted through the DNA replication fork in S phase (6). In principle, the newly deposited nucleosomes could contain entirely old or newly synthesized histone proteins, or a mixture of both. Accumulating evidence suggests that most H3/H4 tetramers remain intact, with the exception of some H3.3/H4 tetramers, indicating that nucleosomes should contain either new or ...

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“…The CPC is a complex of four subunits, Survivin, Borealin, INCENP, and the Aurora B kinase. Aurora B is an essential kinase, which regulates mitotic progression, including spindle assembly checkpoint, condensation, and chromosomal biorientation and cytokinesis [40][41][42]. Additionally, Aurora B phosphorylates Haspin N-terminus on several sites allowing its over-activation and creating a positive feedback loop triggering the accumulation of CPC at the centromeres [14] (Figure 4 lower panel).…”

Section: Protein Phosphorylation 36mentioning

confidence: 99%

The Mitotic Protein Kinase Haspin and Its Inhibitors

Feizbakhsh¹,

Place²,

Fant³

et al. 2017

Protein Phosphorylation

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Haspin is an atypical serine/threonine protein kinase essential to mitosis. Unlike other protein kinases, its kinase domain does not require phosphorylation in order to be activated and bears very high substrate specificity and selectivity. Few substrates have been identified so far. Haspin phosphorylation on threonine 3 of Histone H3 from prophase to anaphase participates to centromeric Aurora B localization and ensures proper kinetochore-microtubule attachment. Haspin is also involved in the maintenance of centromeric cohesion and the mitotic spindle. Inhibitors have been developed and provided tools to dissect Haspin function. The kinase is now considered as a potential therapeutic target against cancer. We discuss here the latest findings on this essential mitotic protein.

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The chromosomal passenger complex (CPC): from easy rider to the godfather of mitosis

Cited by 794 publications

References 253 publications

Increased Aurora B activity causes continuous disruption of kinetochore–microtubule attachments and spindle instability

Increased Aurora B activity causes continuous disruption of kinetochore–microtubule attachments and spindle instability

Preferential Phosphorylation on Old Histones during Early Mitosis in Human Cells

The Mitotic Protein Kinase Haspin and Its Inhibitors

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