Faculty Opinions recommendation of Mechanism limiting centrosome duplication to once per cell cycle.

Centrosomes play critical roles in the cell division cycle and ciliogenesis. Sfi1 is a centrin-binding protein conserved from yeast to humans. Budding yeast Sfi1 is essential for the initiation of spindle pole body (SPB; yeast centrosome) duplication. However, the recruitment and partitioning of Sfi1 to centrosomal structures have never been fully investigated in any organism, and the presumed importance of the conserved tryptophans in the internal repeats of Sfi1 remains untested. Here we report that in fission yeast, instead of doubling abruptly at the initiation of SPB duplication and remaining at a constant level thereafter, Sfi1 is gradually recruited to SPBs throughout the cell cycle. Like an sfi1Δ mutant, a Trp-to-Arg mutant (sfi1-M46) forms monopolar spindles and exhibits mitosis and cytokinesis defects. Sfi1-M46 protein associates preferentially with one of the two daughter SPBs during mitosis, resulting in a failure of new SPB assembly in the SPB receiving insufficient Sfi1. Although all five conserved tryptophans tested are involved in Sfi1 partitioning, the importance of the individual repeats in Sfi1 differs. In summary, our results reveal a link between the conserved tryptophans and Sfi1 partitioning and suggest a revision of the model for SPB assembly.

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Molecular Mechanisms that Restrict Yeast Centrosome Duplication to One Event per Cell Cycle

Current Biology ◽

10.1016/j.cub.2014.05.032 ◽

2014 ◽

Vol 24 (13) ◽

pp. 1456-1466 ◽

Cited By ~ 38

Author(s):

Menattallah Elserafy ◽

Mirela Šarić ◽

Annett Neuner ◽

Tien-chen Lin ◽

Wanlu Zhang ◽

...

Keyword(s):

Cell Cycle ◽

Molecular Mechanisms ◽

Centrosome Duplication

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Expression of Golgi Membrane Protein p138 is Cell Cycle-independent and Dissociated from Centrosome Duplication

Cell Structure and Function ◽

10.1247/csf.27.117 ◽

2002 ◽

Vol 27 (2) ◽

pp. 117-117 ◽

Cited By ~ 4

Author(s):

Kohei Doi ◽

Shohei Noma ◽

Fumiaki Yamao ◽

Hideki Goko ◽

Tatsuo Yagura

Keyword(s):

Cell Cycle ◽

Membrane Protein ◽

Centrosome Duplication ◽

Golgi Membrane

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Casein Kinase II is Required for Proper Cell Division and Acts as a Negative Regulator of Centrosome Duplication in C. elegans Embryos

10.1101/083378 ◽

2016 ◽

Author(s):

Jeffrey C. Medley ◽

Megan M. Kabara ◽

Michael D. Stubenvoll ◽

Lauren E. DeMeyer ◽

Mi Hye Song

Keyword(s):

Cell Cycle ◽

Cell Division ◽

Cell Cycle Progression ◽

Casein Kinase Ii ◽

Casein Kinase ◽

Negative Regulator ◽

Centrosome Duplication ◽

Dependent Manner ◽

C Elegans ◽

Mother Centriole

Summary statementThe conserved protein kinase CK2 negatively regulates centrosome assembly and is required for proper cell cycle progression and cytokinesis in early C. elegans embryos.AbstractCentrosomes are the primary microtubule-organizing centers that orchestrate microtubule dynamics during the cell cycle. The correct number of centrosomes is pivotal for establishing bipolar mitotic spindles that ensure accurate segregation of chromosomes. Thus, centrioles must duplicate once per cell cycle, one daughter per mother centriole, the process of which requires highly coordinated actions among core factors and modulators. Protein phosphorylation is shown to regulate the stability, localization and activity of centrosome proteins. Here, we report the function of Casein Kinase II (CK2) in early C. elegans embryos. The catalytic subunit (KIN-3/CK2α) of CK2 localizes to nuclei, centrosomes and midbodies. Inactivating CK2 leads to cell division defects, including chromosome missegregation, cytokinesis failure and aberrant centrosome behavior. Furthermore, depletion or inhibiting kinase activity of CK2 results in elevated ZYG-1 levels at centrosomes, restoring centrosome duplication and embryonic viability to zyg-1 mutants. Our data suggest that CK2 functions in cell division and negatively regulates centrosome duplication in a kinase-dependent manner.

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Loss of the conserved Alveolate kinase MAPK2 decouples Toxoplasma cell growth from the cell cycle

10.1101/2020.05.13.095091 ◽

2020 ◽

Author(s):

Xiaoyu Hu ◽

William J. O’Shaughnessy ◽

Tsebaot G. Beraki ◽

Michael L. Reese

Keyword(s):

Cell Cycle ◽

Toxoplasma Gondii ◽

Protein Kinases ◽

Daughter Cell ◽

Protozoan Parasite ◽

Productive Infection ◽

Centrosome Duplication ◽

Loss Of Function ◽

Mitogen Activated Protein ◽

Parasite Replication

AbstractMitogen-activated protein kinases (MAPKs) are a conserved family of protein kinases that regulate signal transduction, proliferation, and development throughout eukaryotes. The Apicomplexan parasite Toxoplasma gondii expresses three MAPKs. Two of these, ERK7 and MAPKL1, have been respectively implicated in the regulation of conoid biogenesis and centrosome duplication. The third kinase, MAPK2, is specific to and conserved throughout Alveolata, though its function is unknown. We used the auxin-inducible degron system to determine phenotypes associated with MAPK2 loss-of-function in Toxoplasma. We observed that parasites lacking MAPK2 failed to duplicate their centrosomes and therefore did not initiate daughter-cell budding, which ultimately led to parasite death. MAPKL2-deficient parasites initiated, but did not complete DNA replication, and arrested prior to mitosis. Surprisingly, the parasites continued to grow in size and to replicate their Golgi, mitochondria, and apicoplasts. We found that the failure in centrosome duplication is distinct from the phenotype caused by depletion of MAPKL1. As we did not observe MAPK2 localization at the centrosome at any point in the cell cycle, our data suggest MAPK2 regulates a process at a distal site that is required for completion of centrosome duplication and initiation of parasite mitosis.ImportanceToxoplasma gondii is a ubiquitous intracellular protozoan parasite that can cause severe and fatal disease in immunocompromised patients and the developing fetus. Rapid parasite replication is critical for establishing a productive infection. Here, we demonstrate that a Toxoplasma protein kinase called MAPK2 is conserved throughout Alveolata and essential for parasite replication. We found that parasites lacking MAPK2 protein were defective in the initiation of daughter cell budding and were rendered inviable. Specifically, TgMAPK2 appears to be required for centrosome replication at the basal end of the nucleus, and its loss causes arrest early in parasite division. MAPK2 is unique to Alveolata and not found in metazoa, and likely is a critical component of an essential parasite-specific signaling network.

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Faculty Opinions recommendation of Mechanism limiting centrosome duplication to once per cell cycle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1033610.488972 ◽

2006 ◽

Author(s):

Adam Linstedt

Keyword(s):

Cell Cycle ◽

Centrosome Duplication

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Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication

Molecular Biology of the Cell ◽

10.1091/mbc.e09-06-0505 ◽

2010 ◽

Vol 21 (4) ◽

pp. 547-561 ◽

Cited By ~ 72

Author(s):

James E. Sillibourne ◽

Frederik Tack ◽

Nele Vloemans ◽

An Boeckx ◽

Sathiesan Thambirajah ◽

...

Keyword(s):

Cell Cycle ◽

Kinase Activity ◽

Proteasome Inhibition ◽

Centrosome Duplication ◽

Active Fraction ◽

Kinase Activation ◽

Centriole Duplication ◽

M Phase ◽

Mother Centriole ◽

Daughter Centriole

Centrosome duplication occurs once every cell cycle in a strictly controlled manner. Polo-like kinase 4 (PLK4) is a key regulator of this process whose kinase activity is essential for centriole duplication. Here, we show that PLK4 autophosphorylation of serine S305 is a consequence of kinase activation and enables the active fraction to be identified in the cell. Active PLK4 is detectable on the replicating mother centriole in G1/S, with the proportion of active kinase increasing through interphase to reach a maximum in mitosis. Activation of PLK4 at the replicating daughter centriole is delayed until G2, but a level equivalent to the replicating mother centriole is achieved in M phase. Active PLK4 is regulated by the proteasome, because either proteasome inhibition or mutation of the degron motif of PLK4 results in the accumulation of S305-phosphorylated PLK4. Autophosphorylation probably plays a role in the process of centriole duplication, because mimicking S305 phosphorylation enhances the ability of overexpressed PLK4 to induce centriole amplification. Importantly, we show that S305-phosphorylated PLK4 is specifically sequestered at the centrosome contrary to the nonphosphorylated form. These data suggest that PLK4 activity is restricted to the centrosome to prevent aberrant centriole assembly and sustained kinase activity is required for centriole duplication.

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Cdc25A Serine 123 Phosphorylation Couples Centrosome Duplication with DNA Replication and Regulates Tumorigenesis

Molecular and Cellular Biology ◽

10.1128/mcb.00138-08 ◽

2008 ◽

Vol 28 (24) ◽

pp. 7442-7450 ◽

Cited By ~ 10

Author(s):

Sathyavageeswaran Shreeram ◽

Weng Kee Hee ◽

Dmitry V. Bulavin

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Dna Replication ◽

Cell Cycle Progression ◽

Phosphorylation Site ◽

Centrosome Duplication ◽

Cycle Progression ◽

Cdc25a Phosphatase

ABSTRACT The cell division cycle 25A (Cdc25A) phosphatase is a critical regulator of cell cycle progression under normal conditions and after stress. Stress-induced degradation of Cdc25A has been proposed as a major way of delaying cell cycle progression. In vitro studies pointed toward serine 123 as a key site in regulation of Cdc25A stability after exposure to ionizing radiation (IR). To address the role of this phosphorylation site in vivo, we generated a knock-in mouse in which alanine was substituted for serine 123. The Cdc25 S123A knock-in mice appeared normal, and, unexpectedly, cells derived from them exhibited unperturbed cell cycle and DNA damage responses. In turn, we found that Cdc25A was present in centrosomes and that Cdc25A levels were not reduced after IR in knock-in cells. This resulted in centrosome amplification due to lack of induction of Cdk2 inhibitory phosphorylation after IR specifically in centrosomes. Further, Cdc25A knock-in animals appeared sensitive to IR-induced carcinogenesis. Our findings indicate that Cdc25A S123 phosphorylation is crucial for coupling centrosome duplication to DNA replication cycles after DNA damage and therefore is likely to play a role in the regulation of tumorigenesis.

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