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

Fry, Andrew M.; Mayor, Thibault; Meraldi, Patrick; Stierhof, York‐Dieter; Tanaka, Kayoko; Nigg, Erich A.

doi:10.1083/jcb.141.7.1563

Cited by 412 publications

(471 citation statements)

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“…In contrast, a catalytically inactive mutant of Nek2 does not induce splitting, indicating that this phenotype is dependent on Nek2 kinase activity. Localization studies and biochemical fractionation con¢rmed the importance of this result by demonstrating that Nek2 is a core component of the centrosome throughout the cell cycle [29,30]. Hence, we proposed that Nek2-dependent phosphorylation of centrosomal substrates may stimulate a loss of cohesion between the duplicated centrosomes in late G2.…”

Section: Polo Kinases and Spindle Formationmentioning

confidence: 79%

“…Intriguingly, immunoelectron microscopy performed following either pre-embedding [30] or ultrathin cryosectioning (Fig. 1) shows that C-Nap1 is speci¢cally associated with the proximal end of the two centrioles.…”

Section: Polo Kinases and Spindle Formationmentioning

confidence: 95%

“…The isolated clone represented the carboxy-terminal domain of a 281 kDa novel coiled-coil protein that was subsequently found to be a core component of the centrosome [30]. Hence, we named this protein C-Nap1, for centrosomal Nek2-associated protein 1.…”

Section: Polo Kinases and Spindle Formationmentioning

confidence: 99%

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Protein kinases in control of the centrosome cycle

et al. 1999

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The centrosome is the major microtubule nucleating center of the animal cell and forms the two poles of the mitotic spindle upon which chromosomes are segregated. During the cell division cycle, the centrosome undergoes a series of major structural and functional transitions that are essential for both interphase centrosome function and mitotic spindle formation. The localization of an increasing number of protein kinases to the centrosome has revealed the importance of protein phosphorylation in controlling many of these transitions. 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.z 1999 Federation of European Biochemical Societies.

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Section: Polo Kinases and Spindle Formationmentioning

confidence: 79%

Section: Polo Kinases and Spindle Formationmentioning

confidence: 95%

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Protein kinases in control of the centrosome cycle

et al. 1999

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“…NEK2 is regulated through the cell cycle (Schultz et al, 1994;Fry et al, 1995) and has been localized to, and been shown to regulate, the centrosome (Fry et al, 1998b;Uto and Sagata, 2000) through interactions with the centrosomal protein C-nap1 (Fry et al, 1998a) and protein phosphatase type 1 (Helps et al, 2000). Additional roles for NEK2 during cell cycle progression are suggested by the localization of NEK2 to meiotic (Rhee and Wolgemuth, 1997) and mitotic chromosomes (Ha et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

Osmani

Davies

Oakley

et al. 2003

MBoC

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The tinA gene of Aspergillus nidulans encodes a protein that interacts with the NIMA mitotic protein kinase in a cell cycle-specific manner. Highly similar proteins are encoded in Neurospora crassa and Aspergillus fumigatus. TINA and NIMA preferentially interact in interphase and larger forms of TINA are generated during mitosis. Localization studies indicate that TINA is specifically localized to the spindle pole bodies only during mitosis in a microtubule-dependent manner. Deletion of tinA alone is not lethal but displays synthetic lethality in combination with the anaphase-promoting complex/cyclosome mutation bimE7. At the bimE7 metaphase arrest point, lack of TINA enhanced the nucleation of bundles of cytoplasmic microtubules from the spindle pole bodies. These microtubules interacted to form spindles joined in series via astral microtubules as revealed by live cell imaging. Because TINA is modified and localizes to the spindle pole bodies at mitosis, and lack of TINA causes enhanced production of cytoplasmic microtubules at metaphase arrest, we suggest TINA is involved in negative regulation of the astral microtubule organizing capacity of the spindle pole bodies during metaphase. INTRODUCTIONMitosis is regulated by cell cycle-specific phosphorylation and regulated proteolysis of regulatory proteins mediated by activation and inactivation of cyclin-dependent kinases (CDKs) (O'Farrell, 2001) in all eukaryotes, including Aspergillus nidulans . In A. nidulans, mitosis is also regulated by a second kinase, NIMA (never in mitosis A), which when inactivated arrests cell in G 2 even though the CDK1 complex is active (Osmani et al., 1991a). Without activation of NIMA, active CDK1 is unable to accumulate in the nucleus but does so after mutation of the nuclear pore complex protein SONA rae1/gle2 (Wu et al., 1998). NIMA may therefore interact with the nuclear pore complex to help mediate localization of CDK1 at mitosis.NIMA is regulated at multiple levels, including mRNA abundance (Osmani et al., 1987), phosphorylation , and proteolysis Ye et al., 1998). NIMA has also been shown to have a dynamic localization during mitosis being sequentially located to DNA, the mitotic spindle, and the spindle pole body (SPB) (De Souza et al., 2000).Expression of NIMA promotes chromatin condensation (O'Connell et al., 1994) and transient formation of mitotic spindle-like structures (Osmani et al., 1988b). Stable versions of NIMA prevent normal exit from mitosis . The mitotic promoting activity of NIMA crosses species barriers from yeast to humans (Lu and Hunter, 1995a), indicating conserved NIMA substrates are involved in mitotic regulation.NIMA-related kinases have been isolated from Neurospora crassa and Schizosaccharomyces pombe (Krien et al., 1998), and the S. pombe NIMA-like kinase Fin1p is involved in mitotic regulation (Grallert and Hagan, 2002;Krien et al., 2002). NIMA-related kinases (NEKs) have also been identified in higher eukaryotes (Letwin et al., 1992;Schultz and Nigg, 1993;Lu and Hunter, 1995b;Chen et al., 1999;Tana...

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“…The mitotic functions of NIMA are conserved in eukaryotic cells, with NIMA being the founding member of the family of NIMA-related kinases called the Nek kinases (Fry et al 2012). Human Nek kinases have been shown to share NIMA's function in regulating the bipolar spindle formation as well as the permeability of the nuclear envelope at mitotic entry (Fry et al 1998;Bahe et al 2005;Bahmanyar et al 2008;Bertran et al 2011;Laurell et al 2011). Consistent with these conserved functions, ectopic expression of NIMA in organisms such as fission yeast, Xenopus, and human cells results in premature mitotic characteristics, including chromatin condensation (O'Connell et al 1994;Lu and Hunter 1995).…”

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confidence: 99%

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast.D URING the transition from interphase into mitosis, chromatin undergoes dramatic global restructuring to go from a relaxed interphase configuration amenable to gene expression to a condensed form characteristic of mitotic chromosomes. Chromatin condensation not only marks mitosis but is also essential for the normal segregation of the duplicated sister chromatids into daughter nuclei. On the other hand, during mitotic exit, decondensation of chromatin needs to be triggered in a correct temporal manner to enable successful transition into interphase. In Aspergillus nidulans, a model filamentous fungus that enabled discovery of cell cycle-specific genes, mitotic initiation requires the function of the essential NIMA mitotic kinase (Oakley and Morris 1983;Osmani et al. 1987). Early evidence pointed to a role for NIMA in regulating chromatin compaction through the cell cycle since overexpression of NIMA was sufficient to induce chromatin condensation independent of cell cycle phase (Osmani et al. 1988;. Importantly, NIMA is required for, and can promote, the phosphorylation of histone H3 at serine 10 (De Souza et al. 2000), a universal marker of mitotic chromatin. In addition, NIMA has been shown to regulate the partial disassembly of nuclear pore complexes, allowing the access of mitotic regulators to the nucleus (Wu et al. 1998;De S...

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

Cited by 412 publications

References 64 publications

Protein kinases in control of the centrosome cycle

Protein kinases in control of the centrosome cycle

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

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