Andrew M Fry

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..Here, we review the functions of the human NEKs, with particular emphasis on those family members that are involved in cell cycle control, and consider their potential as therapeutic targets in cancer...

..The direct interaction of substrates with core subunits of the APC/C could allow their degradation to proceed unhindered even when the SAC is active...

..Furthermore, we highlight their potential as novel chemotherapeutic targets...

..Degradation of the APC/C activator Cdc20 seems to be an essential and conserved mechanism to maintain this checkpoint in the presence of chromosomes that are not attached to the mitotic spindle...

..Recent studies in lower organisms have raised the possibility that kinases related to Nek2 may have conserved functions in MTOC organization, as well as in other aspects of mitotic progression...

..Thus, this study reveals not only an important mechanism for the regulation of the Nek2 kinase but, furthermore, highlights an unusual organization of a leucine zipper dimerization motif...

..Hence, these studies demonstrate that X-Nek2B is required for efficient assembly of a functional zygotic centrosome and highlight the possibility of multiple roles for vertebrate Nek2 kinases in the centrosome cycle...

..Based on these data, we propose that Pix1 and Pix2 are microtubule-associated adaptor proteins that likely contribute to a range of developmental and cell division processes...

..We also propose that phosphorylation by Nek2 may prime Nlp for phosphorylation by Plk1...

..Furthermore, this study defines a molecular pathway that may be targeted to prevent centrosome overduplication in S-phase-arrested cancer cells...

..Taken together, these findings reveal important insights into the mechanisms through which Nek8 activity and localization are regulated during ciliogenesis...

..Thus, although Cdc20 is required for the degradation of Nek2A, it is not required for its recruitment and this renders its degradation insensitive to the mitotic checkpoint...

..Together, these data lead us to propose that Nek6 and Nek7 play independent roles not only in robust mitotic spindle formation but also potentially in cytokinesis...

..Together, these data highlight multiple processes involved in regulating the abundance of Nek2 kinase at the centrosome including microtubule binding, the centriolar satellite component PCM-1, and localized protein degradation...

..2006). Phosphorylation of Kiz ensures the integrity of spindle poles in the face of severe pulling forces exerted by the chromosome-attached spindle microtubules...

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..Furthermore, definition of how OFD1 and PCM-1 interact helps explain why different OFD1 mutations lead to clinically variable phenotypes...

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..Our data provide evidence of a physical nuclear-cytoskeletal connection that is likely to be a key mechanism in nuclear-cytoplasmic communication and regulation of nuclear position...

..This has important implications for our understanding of both Nek2 protein kinase regulation and the control of centrosome structure during mitosis...

..These results support a model in which maternal Nek2B acts to promote assembly of a functional zygotic centrosome in a kinase-independent manner...

..Moreover, they indicate that one function of mammalian Nek2 relates to the centrosome cycle and thus provide a new perspective on the role of NIMA-related kinases...

..However, they suggest that loss of centriole cohesion and C-Nap1 displacement may be distinct mitotic events...

..These data highlight the Nek2 kinase as novel potential target for chemotherapeutic intervention in breast cancer...

..Hence, Poc1A and Poc1B play redundant, but essential, roles in generation of stable centrioles, but Poc1B may have additional independent functions during cell cycle progression...

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..As a result, the leucine zipper of Nek2 kinase is the first example where the frameshift of coiled-coil heptad repeats has been directly observed experimentally...

..We conclude that C-Nap1 is a key component of a dynamic, cell cycle-regulated structure that mediates centriole-centriole cohesion...

..We propose that recognition of substrates by the APC/C-Cdc20 in early mitosis depends upon possession of an extended D-box motif...

..Based on these findings, we propose a model implicating both Nek2 and C-Nap1 in the regulation of centriole-centriole cohesion during the cell cycle...

..Thus, oscillation of APC/C activity during cell cycle arrest promotes both centrosome amplification and genome instability...

..Here, we focus on two protein kinases, the polo-like kinase 1 and the NIMA-related kinase 2, for which recent data indicate key roles during the centrosome cycle...

..These results show that Plk2 is a physiological centrosomal protein and that its kinase activity is likely to be required for centriole duplication near the G1-to-S phase transition...

..Thus, alternative splicing provides an unusual mechanism for modulating Nek2 localization, enabling it to have both nuclear and cytoplasmic functions...

..Plx1 phosphorylates XErp1 in vitro at a site that targets XErp1 for degradation upon CSF release. Thus, our data lead to a model of APC/C activation in Xenopus egg extract in which Plx1 targets the APC/C inhibitor XErp1 for degradation...

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