scholarly journals Cyclin A triggers Mitosis either via Greatwall or Cyclin B

2018 ◽  
Author(s):  
Nadia Hégarat ◽  
Adrijana Crncec ◽  
Maria F. Suarez Peredoa Rodri-guez ◽  
Fabio Echegaray Iturra ◽  
Yan Gu ◽  
...  
Keyword(s):  
Cyclin A ◽  
Cyclin B ◽  
Mitotic Progression ◽  
Nuclear Envelope Breakdown ◽  
Distinct Subset ◽  
Initial Activation ◽  
Greatwall Kinase ◽  
G2 Phase ◽  
Higher Eukaryotes ◽  
Complete Cell

AbstractTwo mitotic Cyclins, A and B, exist in higher eukaryotes, but their specialised functions in mitosis are poorly understood. Using degron tags we analyse how acute depletion of these proteins affects mitosis. Loss of Cyclin A in G2-phase prevents the initial activation of Cdk1. Cells lacking Cyclin B can enter mitosis and phosphorylate most mitotic proteins, because of parallel PP2A:B55 phos-phatase inactivation by Greatwall kinase. The final barrier to mitotic establishment corresponds to nuclear envelope breakdown that requires a decisive shift in the balance of Cdk1 and PP2A:B55 activity. Beyond this point Cyclin B/Cdk1 is essential to phosphorylate a distinct subset mitotic Cdk1 substrates that are essential to complete cell division. Our results identify how Cyclin A, B and Greatwall coordinate mitotic progression by increasing levels of Cdk1-dependent substrate phos-phorylation.

scholarly journals Cyclin B–Cdk1 inhibits protein phosphatase PP2A-B55 via a Greatwall kinase–independent mechanism

2014 ◽  
Vol 204 (6) ◽  
pp. 881-889 ◽  
Author(s):  
Eiichi Okumura ◽  
Atsushi Morita ◽  
Mizuho Wakai ◽  
Satoru Mochida ◽  
Masatoshi Hara ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Cyclin B ◽  
Mitotic Progression ◽  
Independent Mechanism ◽  
M Phase ◽  
Dependent Inhibition ◽  
Phosphatase 2A ◽  
Initial Activation ◽  
Greatwall Kinase ◽  
Different Levels

Entry into M phase is governed by cyclin B–Cdk1, which undergoes both an initial activation and subsequent autoregulatory activation. A key part of the autoregulatory activation is the cyclin B–Cdk1–dependent inhibition of the protein phosphatase 2A (PP2A)–B55, which antagonizes cyclin B–Cdk1. Greatwall kinase (Gwl) is believed to be essential for the autoregulatory activation because Gwl is activated downstream of cyclin B–Cdk1 to phosphorylate and activate α-endosulfine (Ensa)/Arpp19, an inhibitor of PP2A-B55. However, cyclin B–Cdk1 becomes fully activated in some conditions lacking Gwl, yet how this is accomplished remains unclear. We show here that cyclin B–Cdk1 can directly phosphorylate Arpp19 on a different conserved site, resulting in inhibition of PP2A-B55. Importantly, this novel bypass is sufficient for cyclin B–Cdk1 autoregulatory activation. Gwl-dependent phosphorylation of Arpp19 is nonetheless necessary for downstream mitotic progression because chromosomes fail to segregate properly in the absence of Gwl. Such a biphasic regulation of Arpp19 results in different levels of PP2A-B55 inhibition and hence might govern its different cellular roles.

scholarly journals Cyclin A triggers Mitosis either via the Greatwall kinase pathway or Cyclin B

2020 ◽  
Vol 39 (11) ◽  
Author(s):  
Nadia Hégarat ◽  
Adrijana Crncec ◽  
Maria F Suarez Peredo Rodriguez ◽  
Fabio Echegaray Iturra ◽  
Yan Gu ◽  
...  
Keyword(s):  
Cyclin A ◽  
Cyclin B ◽  
Greatwall Kinase ◽  
Kinase Pathway

scholarly journals Activation of the Xenopus cyclin degradation machinery by full-length cyclin A

1996 ◽  
Vol 109 (5) ◽  
pp. 1071-1079 ◽  
Author(s):  
C. Jones ◽  
C. Smythe
Keyword(s):  
Protein Synthesis ◽  
Dna Replication ◽  
Kinase Activity ◽  
Cyclin A ◽  
Cell Types ◽  
Cyclin B1 ◽  
Full Length ◽  
Cyclin B ◽  
Cdc2 Kinase ◽  
Nuclear Envelope Breakdown

The entry into mitosis is dependent on the activation of mitotic forms of cdc2 kinase. In many cell types, cyclin A-associated kinase activity peaks just prior to that of cyclin B, although the precise role of cyclin A-associated kinase in the entry into mitosis is still unclear. Previous work has suggested that while cyclin B is capable of triggering cyclin destruction in Xenopus cell-free systems, cyclin A-associated kinase is not able to support this function. Here we have expressed a full-length human cyclin A in Escherichia coli and purified the protein to homogeneity by virtue of an N-terminal histidine tag. We have found that when added to Xenopus cell-free extracts free of cyclin B and incapable of protein synthesis, the temporal pattern of cyclin A-associated cdc2 kinase activity showed distinct differences that were dependent on the concentration of cyclin A added. When cyclin A was added to a concentration that generated levels of cdc2 kinase activity capable of inducing nuclear envelope breakdown, the histone H1 kinase activity profile was bi-phasic, consisting of an activation phase followed by an inactivation phase. Inactivation was found to be due to cyclin destruction, which was prevented by mos protein. Cyclin destruction was followed by nuclear reassembly and an additional round of DNA replication, indicating that there is no protein synthesis requirement for DNA replication in this embryonic system. It has been suggested that the evolutionary recruitment of cyclin A into an S phase function may have necessitated the loss of an original mitotic ability to activate the cyclin destruction pathway. The results presented here indicate that cyclin A has not lost the ability to activate its own destruction and that cyclin A-mediated activation of the cyclin destruction pathway permitted destruction of cyclin B1 as well as cyclin A, indicating that there are not distinct cyclin A and cyclin B destruction pathways. Thus the ordered progression of the cell cycle requires the careful titration of cyclin. A concentration in order to avoid activation of the cyclin destruction pathway before sufficient active cyclin B/cdc2 kinase has accumulated.

scholarly journals Cyclins A and B associate with chromatin and the polar regions of spindles, respectively, and do not undergo complete degradation at anaphase in syncytial Drosophila embryos.

1992 ◽  
Vol 116 (4) ◽  
pp. 967-976 ◽  
Author(s):  
G Maldonado-Codina ◽  
D M Glover
Keyword(s):  
Metaphase Plate ◽  
Cyclin A ◽  
Cyclin B ◽  
Drosophila Embryo ◽  
Polar Regions ◽  
Surface Layers ◽  
Nuclear Envelope Breakdown ◽  
Apical Side ◽  
Punctate Staining ◽  
Drosophila Embryos

Maternally contributed cyclin A and B proteins are initially distributed uniformly throughout the syncytial Drosophila embryo. As dividing nuclei migrate to the cortex of the embryo, the A and B cyclins become concentrated in surface layers extending to depths of approximately 30-40 microns and 5-10 microns, respectively. The initiation of nuclear envelope breakdown, spindle formation, and the initial congression of the centromeric regions of the chromosomes onto the metaphase plate all take place within the surface layer occupied by cyclin B on the apical side of the blastoderm nuclei. Cyclin B is seen mainly, but not exclusively, in the vicinity of microtubules throughout the mitotic cycle. It is most conspicuous around the centrosomes. Cyclin A is present at its highest concentrations throughout the cytoplasm during the interphase periods of the blastoderm cycles, although weak punctate staining can also be detected in the nucleus. It associates with the condensing chromosomes during prophase, segregates into daughter nuclei in association with chromosomes during anaphase, to redistribute into the cytoplasm after telophase. In contrast to the cycles following cellularization, neither cyclin is completely degraded upon the metaphase-anaphase transition.

scholarly journals Fcp1 phosphatase controls Greatwall kinase to promote PP2A-B55 activation and mitotic progression

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Rosa Della Monica ◽  
Roberta Visconti ◽  
Nando Cervone ◽  
Angela Flavia Serpico ◽  
Domenico Grieco
Keyword(s):  
Cell Division ◽  
Protein Phosphorylation ◽  
Kinase Activity ◽  
Protein Phosphatases ◽  
Human Cells ◽  
Cyclin B ◽  
Major Protein ◽  
Phosphorylation Sites ◽  
Mitotic Progression ◽  
Greatwall Kinase

During cell division, progression through mitosis is driven by a protein phosphorylation wave. This wave namely depends on an activation-inactivation cycle of cyclin B-dependent kinase (Cdk) 1 while activities of major protein phosphatases, like PP1 and PP2A, appear directly or indirectly repressed by Cdk1. However, how Cdk1 inactivation is coordinated with reactivation of major phosphatases at mitosis exit still lacks substantial knowledge. We show here that activation of PP2A-B55, a major mitosis exit phosphatase, required the phosphatase Fcp1 downstream Cdk1 inactivation in human cells. During mitosis exit, Fcp1 bound Greatwall (Gwl), a Cdk1-stimulated kinase that phosphorylates Ensa/ARPP19 and converts these proteins into potent PP2A-B55 inhibitors during mitosis onset, and dephosphorylated it at Cdk1 phosphorylation sites. Fcp1-catalyzed dephosphorylation drastically reduced Gwl kinase activity towards Ensa/ARPP19 promoting PP2A-B55 activation. Thus, Fcp1 coordinates Cdk1 and Gwl inactivation to derepress PP2A-B55, generating a dephosphorylation switch that drives mitosis progression.

scholarly journals Specialized Roles of the Two Mitotic Cyclins in Somatic Cells: Cyclin A as an Activator of M Phase–promoting Factor

2007 ◽  
Vol 18 (5) ◽  
pp. 1861-1873 ◽  
Author(s):  
Tsz Kan Fung ◽  
Hoi Tang Ma ◽  
Randy Y.C. Poon
Keyword(s):  
Critical Role ◽  
Cyclin A ◽  
Cyclin B ◽  
Bistable System ◽  
Down Regulation ◽  
Phase Arrest ◽  
M Phase ◽  
G2 Phase ◽  
Outstanding Issue

The role of cyclin B-CDC2 as M phase-promoting factor (MPF) is well established, but the precise functions of cyclin A remain a crucial outstanding issue. Here we show that down-regulation of cyclin A induces a G2 phase arrest through a checkpoint-independent inactivation of cyclin B-CDC2 by inhibitory phosphorylation. The phenotype is rescued by expressing cyclin A resistant to the RNA interference. In contrast, down-regulation of cyclin B disrupts mitosis without inactivating cyclin A-CDK, indicating that cyclin A-CDK acts upstream of cyclin B-CDC2. Even when ectopically expressed, cyclin A cannot replace cyclin B in driving mitosis, indicating the specific role of cyclin B as a component of MPF. Deregulation of WEE1, but not the PLK1-CDC25 axis, can override the arrest caused by cyclin A knockdown, suggesting that cyclin A-CDK may tip the balance of the cyclin B-CDC2 bistable system by initiating the inactivation of WEE1. These observations show that cyclin A cannot form MPF independent of cyclin B and underscore a critical role of cyclin A as a trigger for MPF activation.

scholarly journals Myt1 inhibition of Cyclin A/Cdk1 is essential for fusome integrity and premeiotic centriole engagement in Drosophila spermatocytes

2016 ◽  
Vol 27 (13) ◽  
pp. 2051-2063 ◽  
Author(s):  
Ramya Varadarajan ◽  
Joseph Ayeni ◽  
Zhigang Jin ◽  
Ellen Homola ◽  
Shelagh D. Campbell
Keyword(s):  
Ectopic Expression ◽  
Cyclin A ◽  
Male Meiosis ◽  
Cyclin B ◽  
Cycle Arrest ◽  
Phase Coordinates ◽  
Multipolar Spindles ◽  
M Phase ◽  
G2 Phase ◽  
Regulation Of Cell Cycle

Regulation of cell cycle arrest in premeiotic G2 phase coordinates germ cell maturation and meiotic cell division with hormonal and developmental signals by mechanisms that control Cyclin B synthesis and inhibitory phosphorylation of the M-phase kinase, Cdk1. In this study, we investigated how inhibitory phosphorylation of Cdk1 by Myt1 kinase regulates premeiotic G2 phase of Drosophila male meiosis. Immature spermatocytes lacking Myt1 activity exhibit two distinct defects: disrupted intercellular bridges (fusomes) and premature centriole disengagement. As a result, the myt1 mutant spermatocytes enter meiosis with multipolar spindles. These myt1 defects can be suppressed by depletion of Cyclin A activity or ectopic expression of Wee1 (a partially redundant Cdk1 inhibitory kinase) and phenocopied by expression of a Cdk1F mutant defective for inhibitory phosphorylation. We therefore conclude that Myt1 inhibition of Cyclin A/Cdk1 is essential for normal fusome behavior and centriole engagement during premeiotic G2 arrest of Drosophila male meiosis. The novel meiotic functions we discovered for Myt1 kinase are spatially and temporally distinct from previously described functions of Myt1 as an inhibitor of Cyclin B/Cdk1 to regulate G2/MI timing.

The Polo-like kinase Plx1 is a component of the MPF amplification loop at the G2/M-phase transition of the cell cycle in Xenopus eggs

1998 ◽  
Vol 111 (12) ◽  
pp. 1751-1757 ◽  
Author(s):  
A. Abrieu ◽  
T. Brassac ◽  
S. Galas ◽  
D. Fisher ◽  
J.C. Labbe ◽  
...  
Keyword(s):  
Phase Transition ◽  
Cell Cycle ◽  
Cyclin A ◽  
Cyclin B ◽  
Cdc2 Kinase ◽  
C Terminus ◽  
M Phase ◽  
Egg Extracts ◽  
Amplification Loop

We have investigated whether Plx1, a kinase recently shown to phosphorylate cdc25c in vitro, is required for activation of cdc25c at the G2/M-phase transition of the cell cycle in Xenopus. Using immunodepletion or the mere addition of an antibody against the C terminus of Plx1, which suppressed its activation (not its activity) at G2/M, we show that Plx1 activity is required for activation of cyclin B-cdc2 kinase in both interphase egg extracts receiving recombinant cyclin B, and cycling extracts that spontaneously oscillate between interphase and mitosis. Furthermore, a positive feedback loop allows cyclin B-cdc2 kinase to activate Plx1 at the G2/M-phase transition. In contrast, activation of cyclin A-cdc2 kinase does not require Plx1 activity, and cyclin A-cdc2 kinase fails to activate Plx1 and its consequence, cdc25c activation in cycling extracts.

scholarly journals SGK phosphorylates Cdc25 and Myt1 to trigger cyclin B–Cdk1 activation at the meiotic G2/M transition

2019 ◽  
Vol 218 (11) ◽  
pp. 3597-3611 ◽  
Author(s):  
Daisaku Hiraoka ◽  
Enako Hosoda ◽  
Kazuyoshi Chiba ◽  
Takeo Kishimoto
Keyword(s):  
Somatic Cell ◽  
Cyclin A ◽  
Pi3k Pathway ◽  
Cyclin B ◽  
Hormonal Stimulation ◽  
Oocyte Meiosis ◽  
M Phase ◽  
Mitosis And Meiosis ◽  
Cell Mitosis ◽  
Stimulation Of

The kinase cyclin B–Cdk1 complex is a master regulator of M-phase in both mitosis and meiosis. At the G2/M transition, cyclin B–Cdk1 activation is initiated by a trigger that reverses the balance of activities between Cdc25 and Wee1/Myt1 and is further accelerated by autoregulatory loops. In somatic cell mitosis, this trigger was recently proposed to be the cyclin A–Cdk1/Plk1 axis. However, in the oocyte meiotic G2/M transition, in which hormonal stimuli induce cyclin B–Cdk1 activation, cyclin A–Cdk1 is nonessential and hence the trigger remains elusive. Here, we show that SGK directly phosphorylates Cdc25 and Myt1 to trigger cyclin B–Cdk1 activation in starfish oocytes. Upon hormonal stimulation of the meiotic G2/M transition, SGK is activated by cooperation between the Gβγ-PI3K pathway and an unidentified pathway downstream of Gβγ, called the atypical Gβγ pathway. These findings identify the trigger in oocyte meiosis and provide insights into the role and activation of SGK.

scholarly journals Both cyclin A delta 60 and B delta 97 are stable and arrest cells in M-phase, but only cyclin B delta 97 turns on cyclin destruction.

1991 ◽  
Vol 10 (13) ◽  
pp. 4311-4320 ◽  
Author(s):  
F.C. Luca ◽  
E.K. Shibuya ◽  
C.E. Dohrmann ◽  
J.V. Ruderman
Keyword(s):  
Cyclin A ◽  
Cyclin B ◽  
M Phase
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