Insights into Anaphase Promoting Complex TPR subdomain assembly from a CDC26–APC6 structure

Departments of Structural Biology and Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Nature Structural & Molecular Biology (Impact Factor: 13.31). 09/2009; 16(9):987-9. DOI: 10.1038/nsmb.1645
Source: PubMed

ABSTRACT The multisubunit anaphase promoting complex (APC) is an essential cell-cycle regulator. Although CDC26 is known to have a role in APC assembly, its molecular function has remained unclear. Biophysical, structural and genetic studies presented here reveal that CDC26 stabilizes the structure of APC6, a core TPR protein required for APC integrity. Notably, CDC26-APC6 association involves an intermolecular TPR mimic composed of one helix from each protein.

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    • "LOC641788 encodes a protein similar to the CDC26 subunit of the anaphase promoting complex (APC), an essential cell-cycle regulator. [43] It regulates by promoting ubiquitin-mediated proteolysis of key cell cycle regulatory proteins. Finally, STAT 4 is a signal transducer and activator of transcription. "
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    PLoS ONE 07/2014; 9(7):e103523. DOI:10.1371/journal.pone.0103523 · 3.23 Impact Factor
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    • "Extensive coverage of these re­ cent efforts is to be found in several recent reviews (Peters, 2006; Barford, 2011a,b; Pines, 2011). Progress in the structural investigation of the APC/C is being brought forward through hybrid approaches that combine biochemical reconstitution, x­ray crystallography of subdomains, negative stain and cryo­ EM, mass spectrometry, nuclear magnetic resonance, and cross­ linking analysis (Gieffers et al., 2001; Wendt et al., 2001; Au et al., 2002; Dube et al., 2005; Passmore et al., 2005; Thornton et al., 2006; Ohi et al., 2007; Herzog et al., 2009; Wang et al., 2009; Zhang et al., 2010a,b; Buschhorn et al., 2011; da Fonseca et al., 2011; Schreiber et al., 2011; Chao et al., 2012; Tian et al., 2012; Uzunova et al., 2012; Zhang et al., 2013). A recently pro­ posed pseudoatomic model of the APC/C (Fig. 2, A–D), together with medium­resolution analyses of APC/C complexes with acti­ vator subunits or spindle checkpoint inhibitors, provide an invalu­ able new framework for understanding the molecular details of APC/C function (Dube et al., 2005; Ohi et al., 2007; Herzog et al., 2009; Buschhorn et al., 2011; da Fonseca et al., 2011; Schreiber et al., 2011). "
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    ABSTRACT: The anaphase-promoting complex or cyclosome (APC/C) is a conserved, multisubunit E3 ubiquitin (Ub) ligase that is active both in dividing and in postmitotic cells. Its contributions to life are especially well studied in the domain of cell division, in which the APC/C lies at the epicenter of a regulatory network that controls the directionality and timing of cell cycle events. Biochemical and structural work is shedding light on the overall organization of APC/C subunits and on the mechanism of substrate recognition and Ub chain initiation and extension as well as on the molecular mechanisms of a checkpoint that seizes control of APC/C activity during mitosis. Here, we review how these recent advancements are modifying our understanding of the APC/C.
    The Journal of Cell Biology 04/2013; 201(2):177-89. DOI:10.1083/jcb.201301130 · 9.83 Impact Factor
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    • "In addition, the extensive surface generated by OGT is likely to represent several overlapping binding pockets which can accommodate multiple substrates (Fig. 6A). Furthermore, partner binding can rely on a mechanism similar to the mode of binding described earlier, in the case of CDC26 bound to APC6 (see Fig. 4C) (Wang et al. 2009). "
    Protein Interactions, 03/2012; , ISBN: 978-953-51-0244-1
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