Binding of
            <i>Drosophila</i>
            Polo kinase to its regulator Matrimony is noncanonical and involves two separate functional domains

Bonner, Amanda M.; Hughes, Stacie E.; Chisholm, Jennifer; Smith, S. Kendall; Slaughter, Brian D.; Unruh, Jay R.; Collins, Kimberly A.; Friederichs, Jennifer M.; Florens, Laurence; Swanson, Selene K.; Pelot, Marissa C.; Miller, Danny E.; Washburn, Michael P.; Jaspersen, Sue L.; Hawley, R. Scott

doi:10.1073/pnas.1301690110

Cited by 28 publications

(55 citation statements)

References 36 publications

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“…Paradoxically the pI shift between the foci appears to be much larger than expected for the addition of a single phosphate group. In contrast, our own analysis of S2R+ cells identified multiple Cnn-LF foci with an average pI shift between foci of 0.2, consistent with the addition of multiple single phosphate groups to the Cnn-PA splice variant, precisely as predicted by ProMoST (Bonner et al 2013) (http://proteomics.mcw. edu/promost.html) (also see Figure S2).…”

Section: Discussionmentioning

confidence: 71%

“…High-affinity binding sites have a proline at the +1 position but an in-depth analysis of Plk1 target substrates found 30% of targets had low-affinity sites, suggesting the binding sites were primed by a kinase other than CDK1 or did not require phosphopriming (Santamaria et al 2011). Additionally, the Polo inhibitor Map205 binds to Polo at the PBD but does not require phosphopriming (Archambault et al 2008) and the encoded inhibitor Matrimony binds to Polo via a noncanonical mechanism (Bonner et al 2013). Clearly Polo can interact with target substrates by more than one mechanism.…”

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confidence: 99%

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An Amino-Terminal Polo Kinase Interaction Motif Acts in the Regulation of Centrosome Formation and Reveals a Novel Function for centrosomin (cnn) in Drosophila

Eisman¹,

Phelps²

2015

Genetics

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The formation of the pericentriolar matrix (PCM) and a fully functional centrosome in syncytial Drosophila melanogaster embryos requires the rapid transport of Cnn during initiation of the centrosome replication cycle. We show a Cnn and Polo kinase interaction is apparently required during embryogenesis and involves the exon 1A-initiating coding exon, suggesting a subset of Cnn splice variants is regulated by Polo kinase. During PCM formation exon 1A Cnn-Long Form proteins likely bind Polo kinase before phosphorylation by Polo for Cnn transport to the centrosome. Loss of either of these interactions in a portion of the total Cnn protein pool is sufficient to remove native Cnn from the pool, thereby altering the normal localization dynamics of Cnn to the PCM. Additionally, Cnn-Short Form proteins are required for polar body formation, a process known to require Polo kinase after the completion of meiosis. Exon 1A Cnn-LF and Cnn-SF proteins, in conjunction with Polo kinase, are required at the completion of meiosis and for the formation of functional centrosomes during early embryogenesis. KEYWORDS Drosophila; centrosomin (cnn); Polo kinase; meiosis; cleavage mitosis T HE animal centrosome is the dominant microtubuleorganizing center (MTOC) in cells and is composed of a centrally located pair of centrioles surrounded by the pericentriolar matrix (PCM). In Drosophila melanogaster, Centrosomin (Cnn) is the most abundant protein in the PCM (Lange et al. 2000) and is required for the localization of many other PCM components during mitosis (Megraw et al. 1999; VaizelOhayon and Schejter 1999). The cnn gene is transcriptionally complex, using three promoters with unique initiating coding exons associated with multiple splice variants making up two protein families (Eisman et al. 2009), contrary to its frequent depiction as a single-protein gene. Much of the work on Cnn has been done on the Cnn-Long Form (Cnn-LF) protein family, containing a highly conserved KFC eukaryotic motif required for g-tubulin localization (Fu and Glover 2012) and three insect-specific conserved motifs (Eisman and Kaufman 2013). The gene also utilizes two of its promoters to produce several splice variants of the Cnn-Short Form (Cnn-SF) protein family, which contain the conserved KFC motif (Eisman et al. 2009) and a rapidly evolving coiled-coil carboxy terminus (Eisman and Kaufman 2013). While all members of either protein family are similar, their amino termini vary with respect to the promoter utilized during transcription.Many studies have shown Cnn-LF proteins are the predominant component of the PCM at mitotic centrosomes, based on immunostaining and the live localization of ectopically expressed GFP::Cnn-PA fusion proteins. In syncytial embryos Cnn-LF protein is always present at centrosomes, whereas in cells the protein is detectable only during mitosis. Two studies have shown Cnn-LF localizes to the centrosome during the peak of flare formation, which occurs at the onset of centrosome replication and continues during S phase and ...

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Section: Discussionmentioning

confidence: 71%

mentioning

confidence: 99%

An Amino-Terminal Polo Kinase Interaction Motif Acts in the Regulation of Centrosome Formation and Reveals a Novel Function for centrosomin (cnn) in Drosophila

Eisman¹,

Phelps²

2015

Genetics

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“…Mtrm-T40A is unable to bind Polo, and cannot rescue chromosome nondisjunction in mtrm/+ heterozygotes [28],[38]. In contrast to wild-type Matrimony, expression of Mtrm-T40A did not cause any developmental defects (Figure 5H).…”

Section: Resultsmentioning

confidence: 93%

A Meiosis-Specific Form of the APC/C Promotes the Oocyte-to-Embryo Transition by Decreasing Levels of the Polo Kinase Inhibitor Matrimony

et al. 2013

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“…Previous studies have shown that Plk kinase activity can be limited to brief periods within the cell cycle through mechanisms involving the transcription, localization, degradation, and autoinhibition of the kinase (3,(10)(11)(12)(13). New regulatory mechanisms of Plks continue to be identified (14)(15)(16), making it clear that our understanding of Plk regulation is incomplete.…”

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confidence: 99%

Autoinhibition and relief mechanism for Polo-like kinase 4

Klebba

Buster

McLamarrah

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Polo-like kinase 4 (Plk4) is a master regulator of centriole duplication, and its hyperactivity induces centriole amplification. Homodimeric Plk4 has been shown to be ubiquitinated as a result of autophosphorylation, thus promoting its own degradation and preventing centriole amplification. Unlike other Plks, Plk4 contains three rather than two Polo box domains, and the function of its third Polo box (PB3) is unclear. Here, we performed a functional analysis of Plk4's structural domains. Like other Plks, Plk4 possesses a previously unidentified autoinhibitory mechanism mediated by a linker (L1) near the kinase domain. Thus, autoinhibition is a conserved feature of Plks. In the case of Plk4, autoinhibition is relieved after homodimerization and is accomplished by PB3 and by autophosphorylation of L1. In contrast, autophosphorylation of the second linker promotes separation of the Plk4 homodimer. Therefore, autoinhibition delays the multiple consequences of activation until Plk4 dimerizes. These findings reveal a complex mechanism of Plk4 regulation and activation which govern the process of centriole duplication.autoinhibition | centriole | centrosome | Polo box | Polo-like kinase 4

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Binding of Drosophila Polo kinase to its regulator Matrimony is noncanonical and involves two separate functional domains

Cited by 28 publications

References 36 publications

An Amino-Terminal Polo Kinase Interaction Motif Acts in the Regulation of Centrosome Formation and Reveals a Novel Function for centrosomin (cnn) in Drosophila

An Amino-Terminal Polo Kinase Interaction Motif Acts in the Regulation of Centrosome Formation and Reveals a Novel Function for centrosomin (cnn) in Drosophila

A Meiosis-Specific Form of the APC/C Promotes the Oocyte-to-Embryo Transition by Decreasing Levels of the Polo Kinase Inhibitor Matrimony

Autoinhibition and relief mechanism for Polo-like kinase 4

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