Drosophila PLUTONIUM protein is a specialized cell cycle regulator required at the onset of embryogenesis.

Elfring, Lisa; Axton, J. M.; Fenger, Douglas D.; Page, Andrea W.; Carminati, Janet L.; Orr‐Weaver, Terry L.

doi:10.1091/mbc.8.4.583

Cited by 43 publications

(34 citation statements)

References 28 publications

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“…Proteins were transferred to Immobilon for immunoblotting as described (Tang et al 1998). Antibodies were used at the following dilutions: guinea pig anti-PNG serum (1:2000; Fenger et al 2000), affinity-purified rabbit anti-PLU (1:200; Elfring et al 1997), and guinea pig anti-GNU serum (1:5000).…”

Section: Immunoblottingmentioning

confidence: 99%

The Drosophila cell cycle kinase PAN GU forms an active complex with PLUTONIUM and GNU to regulate embryonic divisions

Lee¹,

Hoewyk²,

Orr‐Weaver³

2003

Genes Dev.

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Early embryonic cell cycles in Drosophila consist of rapidly alternating S and M phases. Three genes, pan gu (png), plutonium (plu), and giant nuclei (gnu) coordinate these early S-M cycles by ensuring adequate Cyclin B protein levels. Mutations in any of these genes result in unregulated DNA replication and a lack of mitosis ("giant nuclei" phenotype). png encodes a serine/threonine protein kinase, and plu and gnu encode small, novel proteins. We show that PNG, PLU, and GNU constitute a novel protein kinase complex that specifically regulates S-M cell cycles. All three proteins are required for PNG kinase activity and are phosphorylated by PNG in vitro. Yeast two-hybrid screening revealed a direct interaction between PNG and PLU, and their co-expression is required for physical association and activation of PNG kinase. Artificial dimerization of PLU via fusion to either GST or FK506 binding protein (in the presence of dimerizing agent) abrogates the requirement for GNU to activate PNG kinase. We propose a model in which GNU normally regulates embryonic cell cycles by promoting transient dimerization of a core PNG/PLU complex, thereby stimulating PNG kinase activity. Protein kinases play crucial regulatory roles in the cell cycle. CDK/cyclin complexes control transitions throughout the cell cycle, and their proper regulation is essential for ensuring the orderly progression of DNA replication and mitosis (for review, see Murray and Hunt 1993). Association of a cyclin subunit with a CDK subunit is needed both for kinase activity and to confer substrate specificity. Thus, one mechanism for control of these kinase complexes involves the accumulation of threshold levels of cyclins via transcription and regulated degradation of cyclin proteins.Modified cell cycles are used to achieve particular developmental goals. Organisms that must undergo rapid embryogenesis, such as marine invertebrates, amphibians, and insects, utilize a streamlined cell cycle in which DNA replication (S phase) and mitosis (M phase) alternate without intervening gaps. The S-M cycles are driven by maternally provided stockpiles of protein and RNA, eliminating a need for gap phases for gene expression or growth (Foe et al. 1993). Zygotic transcription has not yet begun, so the S-M cell cycles differ from the archetypal cell cycle in that they are regulated solely by posttranscriptional mechanisms. In Drosophila embryos, an additional distinction is that the nuclei divide synchronously in a common cytoplasm (syncytium) during the S-M cycles.During the first seven cell cycles of Drosophila embryogenesis, levels of the mitotic Cyclins A and B as well as their partner kinase CDK1 are high due to maternal stockpiling, and no detectable fluctuations in their levels or CDK1 activity occur (Edgar et al. 1994). However, localized degradation of Cyclin B during these early cycles has been reported (Huang and Raff 1999), and injection of a stabilized form of Cyclin B into early embryos causes mitotic arrest (Su et al. 1998). Thus, localized oscillations in ...

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Section: Immunoblottingmentioning

confidence: 99%

The Drosophila cell cycle kinase PAN GU forms an active complex with PLUTONIUM and GNU to regulate embryonic divisions

Lee¹,

Hoewyk²,

Orr‐Weaver³

2003

Genes Dev.

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“…Ya embryos arrest development at the pronuclear stage (Lin and Wolfner, 1991) with nuclei that show abnormal chromatin condensation (Liu et al, 1995). Ya's epistasis to mutations such as gnu (Liu et al, 1997) that affect S/M coordination and result in multiple rounds of DNA replication (Freeman et al, 1986;Freeman and Glover, 1987;Elfring et al, 1997) suggests that arrest of Ya embryos occurs before the initiation of DNA replication. This phenotype is analogous to that of the rhesus monkey zygotes described above.…”

Section: Why Might Ya's Binding To Chromatin Be Important In Developmmentioning

confidence: 99%

TheDrosophilaNuclear Lamina Protein YA Binds to DNA and Histone H2B with Four Domains

Wolfner

2002

MBoC

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Dramatic changes occur in nuclear organization and function during the critical developmental transition from meiosis to mitosis. The Drosophila nuclear lamina protein YA binds to chromatin and is uniquely required for this transition. In this study, we dissected YA's binding to chromatin. We found that YA can bind to chromatin directly and specifically. It binds to DNA but not RNA, with a preference for double-stranded DNA (linear or supercoiled) over single-stranded DNA. It also binds to histone H2B. YA's binding to DNA and histone H2B is mediated by four domains distributed along the length of the YA molecule. A model for YA function at the end of Drosophila female meiosis is proposed.

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“…plu, png and gnu are three genes required maternally to inhibit DNA replication in the unfertilised egg and to couple S phase and mitosis in the subsequent embryonic cleavage cycles (Freeman et al, 1986;Freeman and Glover, 1987;Shamanski and Orr-Weaver, 1991;Axton et al, 1994;Elfring et al, 1997;Fenger et al, 2000). Regardless of embryonic genotype, oocytes, eggs and embryos derived from plu, png or gnu homozygous females will be referred to here as plu, png or gnu oocytes, eggs or embryos.…”

Section: Introductionmentioning

confidence: 99%

“…However, the level of Plu is reduced in null png mutants (Elfring et al, 1997) leaving open the possibility that Plu is a downstream effector of Pan gu. The levels of the mitotic Cyclins A and B and Cdk1 kinase activity are decreased in embryonic extracts mutant for png, gnu or plu (Fenger et al, 2000) providing a link between the giant nuclei phenotype with known cell cycle regulators.…”

Section: Introductionmentioning

confidence: 99%

giant nucleiis essential in the cell cycle transition from meiosis to mitosis

et al. 2003

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At the transition from meiosis to cleavage mitoses, Drosophila requires the cell cycle regulators encoded by the genes, giant nuclei (gnu), plutonium (plu) and pan gu (png). Embryos lacking Gnu protein undergo DNA replication and centrosome proliferation without chromosome condensation or mitotic segregation. We have identified the gnu gene encoding a novel phosphoprotein dephosphorylated by Protein phosphatase 1 at egg activation. Gnu is normally expressed in the nurse cells and oocyte of the ovary and is degraded during the embryonic cleavage mitoses. Ovarian death and sterility result from gnu gain of function. gnu function requires the activity of pan gu and plu.

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Drosophila PLUTONIUM protein is a specialized cell cycle regulator required at the onset of embryogenesis.

Cited by 43 publications

References 28 publications

The Drosophila cell cycle kinase PAN GU forms an active complex with PLUTONIUM and GNU to regulate embryonic divisions

The Drosophila cell cycle kinase PAN GU forms an active complex with PLUTONIUM and GNU to regulate embryonic divisions

TheDrosophilaNuclear Lamina Protein YA Binds to DNA and Histone H2B with Four Domains

giant nucleiis essential in the cell cycle transition from meiosis to mitosis

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