C-Nap1, a Novel Centrosomal Coiled-Coil Protein and Candidate Substrate of the Cell Cycle-regulated Protein Kinase Nek2

doi:10.1083/jcb.141.7.1563

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© The Rockefeller University Press, 0021-9525/1998//1563 $5.00
The Journal of Cell Biology, Volume 141, Number 7, , 1998 1563-1574

Articles

C-Nap1, a Novel Centrosomal Coiled-Coil Protein and Candidate Substrate of the Cell Cycle–regulated Protein Kinase Nek2

Andrew M. Fry^*, Thibault Mayor^*, Patrick Meraldi^*, York-Dieter Stierhof, Kayoko Tanaka^*, and Erich A. Nigg^*

^* Department of Molecular Biology, Sciences II, University of Geneva, CH-1211 Geneva 4, Switzerland; and Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, D-72076 Tübingen, Germany

Nek2 (for NIMA-related kinase 2) is a mammalian cell cycle–regulatedkinase structurally related to the mitotic regulator NIMA ofAspergillus nidulans. In human cells, Nek2 associates withcentrosomes, and overexpression of active Nek2 has drasticconsequences for centrosome structure. Here, we describe themolecular characterization of a novel human centrosomal protein,C-Nap1 (for centrosomal Nek2-associated protein 1), first identifiedas a Nek2-interacting protein in a yeast two-hybrid screen.Antibodies raised against recombinant C-Nap1 produced stronglabeling of centrosomes by immunofluorescence, and immunoelectron microscopy revealed that C-Nap1 is associated specificallywith the proximal ends of both mother and daughter centrioles.On Western blots, anti–C-Nap1 antibodies recognized alarge protein (>250 kD) that was highly enriched in centrosomepreparations. Sequencing of overlapping cDNAs showed that C-Nap1has a calculated molecular mass of 281 kD and comprises extendeddomains of predicted coiled-coil structure. Whereas C-Nap1was concentrated at centrosomes in all interphase cells, immunoreactivityat mitotic spindle poles was strongly diminished. Finally,the COOH-terminal domain of C-Nap1 could readily be phosphorylatedby Nek2 in vitro, as well as after coexpression of the twoproteins in vivo. Based on these findings, we propose a modelimplicating both Nek2 and C-Nap1 in the regulation of centriole–centriolecohesion during the cell cycle.

Abbreviations used in this paper: CDK, cyclin-dependent kinase; C-Nap1, centrosomal Nek2-associated protein 1; IEM, immunoelectron microscopy; INMP, intranuclear matrix protein; Nek2, NIMA-related kinase 2; PCM, pericentriolar material; SPB, spindle pole body; ${gamma}$ -TuRCs, ${gamma}$ -tubulin– containing ring complexes.

Address all correspondence to Erich A. Nigg, Department of Molecular Biology, Sciences II, University of Geneva, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Tel.: +41 22 702 6127. Fax:+41 22 702 6868. E-mail: erich.nigg{at}molbio.unige.ch

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