Article

The chromosomal passenger complex: guiding Aurora-B through mitosis. J Cell Biol

Department of Medical Oncology, University Medical Center, 3584 CG Utrecht, Netherlands.
The Journal of Cell Biology (Impact Factor: 9.69). 07/2006; 173(6):833-7. DOI: 10.1083/jcb.200604032
Source: PubMed

ABSTRACT During mitosis, the chromosomal passenger complex (CPC) orchestrates highly different processes, such as chromosome alignment, histone modification, and cytokinesis. Proper and timely localization of this complex is the key to precise control over the enzymatic core of the CPC, the Aurora-B kinase. We discuss the molecular mechanisms by which the CPC members direct the dynamic localization of the complex throughout cell division. Also, we summarize posttranslational modifications that occur on the CPC and discuss their roles in regulating localization and function of this mitotic complex.

Download full-text

Full-text

Available from: René H Medema, Aug 28, 2015
0 Followers
 · 
84 Views
  • Source
    • "From late prophase to metaphase CPC localizes to the inner centromere, playing a role in formation and stability of the bipolar mitotic spindle, kinetochore assembly, correction of nonbipolar chromosome-spindle attachments, and control of the spindle checkpoint (Figure 3). At the beginning of anaphase CPC relocates to the midzone of the mitotic spindle and to the cell cortex, remaining evident in the midbody of telophasic cells where it modulates the activity of several proteins involved in spindle dynamics, cleavage furrow formation, and completion of cytokinesis (Figure 3) [18, 19, 36, 37]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation.
    International Journal of Endocrinology 07/2014; 2014(3):816430. DOI:10.1155/2014/816430 · 1.52 Impact Factor
  • Source
    • "This underscores that substrate specificity of the Aurora A and Aurora B kinases is predominantly dictated by specific localization of these kinases. Indeed, the prevailing view is that the non-enzymatic subunits of the CPC activate Aurora B and guide it to its different locations in the dividing cell to encounter and phosphorylate substrates and hence to execute its local functions (Carmena et al. 2012b; Vader et al. 2006b). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The ultimate goal of cell division is equal transmission of the duplicated genome to two new daughter cells. Multiple surveillance systems exist that monitor proper execution of the cell division program and as such ensure stability of our genome. One widely studied protein complex essential for proper chromosome segregation and execution of cytoplasmic division (cytokinesis) is the chromosomal passenger complex (CPC). This highly conserved complex consists of Borealin, Survivin, INCENP, and Aurora B kinase, and has a dynamic localization pattern during mitosis and cytokinesis. Not surprisingly, it also performs various functions during these phases of the cell cycle. In this review, we will give an overview of the latest insights into the regulation of CPC localization and discuss if and how specific localization impacts its diverse functions in the dividing cell.
    Chromosoma 10/2013; 123(1-2). DOI:10.1007/s00412-013-0437-6 · 3.26 Impact Factor
  • Source
    • "The CPC associates with chromatin during G2, then moves to the inner centromeres by prometaphase-metaphase. In anaphase, the CPC translocates to the CS MTs and the equatorial cortex [Adams et al., 2000; Vagnarelli and Earnshaw, 2004; Vader et al., 2006; Szafer-Glusman et al., 2011; van der Waal et al., 2012]. The D. melanogaster genome encodes two Borealin paralogs, Borealin-related (Borr) and Australin [Aust; Gao et al., 2008]; the latter replaces Borr in male meiosis. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Cytokinesis separates the genomic material and organelles of a dividing cell equitably into two physically distinct daughter cells at the end of cell division. This highly choreographed process involves coordinated reorganization and regulated action of the actin and microtubule cytoskeletal systems, an assortment of motor proteins, and membrane trafficking components. Due to their large size, the ease with which exquisite cytological analysis may be performed on them, and the availability of numerous mutants and other genetic tools, Drosophila spermatocytes have provided an excellent system for exploring the mechanistic basis for the temporally programmed and precise spatially localized events of cytokinesis. Mutants defective in male meiotic cytokinesis can be easily identified in forward genetic screens by the production of multinucleate spermatids. In addition, the weak spindle assembly checkpoint in spermatocytes, which causes only a small delay of anaphase onset in the presence of unattached chromosomes, allows investigation of whether gene products required for spindle assembly and chromosome segregation are also involved in cytokinesis. Perhaps due to the large size of spermatocytes and the requirement for two rapid-fire rounds of division without intervening S or growth phases during meiosis, male meiotic mutants have also revealed much about molecular mechanisms underlying new membrane addition during cytokinesis. Finally, cell type-specific differences in the events that set up and complete cytokinesis are emerging from comparison of spermatocytes with cells undergoing mitosis either elsewhere in the organism or in tissue culture. © 2012 Wiley Periodicals, Inc.
    Cytoskeleton 11/2012; 69(11). DOI:10.1002/cm.21063 · 3.01 Impact Factor
Show more