scholarly journals Inhibition of Cdc42 during mitotic exit is required for cytokinesis

2013 ◽  
Vol 202 (2) ◽  
pp. 231-240 ◽  
Author(s):  
Benjamin D. Atkins ◽  
Satoshi Yoshida ◽  
Koji Saito ◽  
Chi-Fang Wu ◽  
Daniel J. Lew ◽  
...  
Keyword(s):  
Cell Cycle ◽  
General Feature ◽  
Budding Yeast ◽  
Mitotic Exit ◽  
Division Site ◽  
Polo Kinase ◽  
Cell Cycle Regulator ◽  
P21 Activated Kinase

The role of Cdc42 and its regulation during cytokinesis is not well understood. Using biochemical and imaging approaches in budding yeast, we demonstrate that Cdc42 activation peaks during the G1/S transition and during anaphase but drops during mitotic exit and cytokinesis. Cdc5/Polo kinase is an important upstream cell cycle regulator that suppresses Cdc42 activity. Failure to down-regulate Cdc42 during mitotic exit impairs the normal localization of key cytokinesis regulators—Iqg1 and Inn1—at the division site, and results in an abnormal septum. The effects of Cdc42 hyperactivation are largely mediated by the Cdc42 effector p21-activated kinase Ste20. Inhibition of Cdc42 and related Rho guanosine triphosphatases may be a general feature of cytokinesis in eukaryotes.

scholarly journals A Mathematical Model of Mitotic Exit in Budding Yeast: The Role of Polo Kinase

PLoS ONE ◽  
2012 ◽  
Vol 7 (2) ◽  
pp. e30810 ◽  
Author(s):  
Baris Hancioglu ◽  
John J. Tyson
Keyword(s):  
Mathematical Model ◽  
Budding Yeast ◽  
Mitotic Exit ◽  
Polo Kinase

scholarly journals Novel Role for Cdc14 Sequestration: Cdc14 Dephosphorylates Factors That Promote DNA Replication

2006 ◽  
Vol 27 (3) ◽  
pp. 842-853 ◽  
Author(s):  
Joanna Bloom ◽  
Frederick R. Cross
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Dna Polymerase ◽  
Budding Yeast ◽  
S Phase ◽  
Mitotic Exit ◽  
Checkpoint Protein ◽  
Replication Factors ◽  
Established Role

ABSTRACT The phosphatase Cdc14 is required for mitotic exit in budding yeast. Cdc14 promotes Cdk1 inactivation by targeting proteins that, when dephosphorylated, trigger degradation of mitotic cyclins and accumulation of the Cdk1 inhibitor, Sic1. Cdc14 is sequestered in the nucleolus during most of the cell cycle but is released into the nucleus and cytoplasm during anaphase. When Cdc14 is not properly sequestered in the nucleolus, expression of the S-phase cyclin Clb5 is required for viability, suggesting that the antagonizing activity of Clb5-dependent Cdk1 specifically is necessary when Cdc14 is delocalized. We show that delocalization of Cdc14 combined with loss of Clb5 causes defects in DNA replication. When Cdc14 is not sequestered, it efficiently dephosphorylates a subset of Cdk1 substrates including the replication factors, Sld2 and Dpb2. Mutations causing Cdc14 mislocalization interact genetically with mutations affecting the function of DNA polymerase ε and the S-phase checkpoint protein Mec1. Our findings suggest that Cdc14 is retained in the nucleolus to support a favorable kinase/phosphatase balance while cells are replicating their DNA, in addition to the established role of Cdc14 sequestration in coordinating nuclear segregation with mitotic exit.

scholarly journals Mitotic exit kinase Dbf2 directly phosphorylates chitin synthase Chs2 to regulate cytokinesis in budding yeast

2012 ◽  
Vol 23 (13) ◽  
pp. 2445-2456 ◽  
Author(s):  
Younghoon Oh ◽  
Kuang-Jung Chang ◽  
Peter Orlean ◽  
Carsten Wloka ◽  
Raymond Deshaies ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Mitotic Exit ◽  
Chitin Synthase ◽  
Chitin Synthesis ◽  
Yeast Saccharomyces Cerevisiae ◽  
Ecm Remodeling ◽  
Division Site ◽  
Primary Septum

How cell cycle machinery regulates extracellular matrix (ECM) remodeling during cytokinesis remains poorly understood. In the budding yeast Saccharomyces cerevisiae, the primary septum (PS), a functional equivalent of animal ECM, is synthesized during cytokinesis by the chitin synthase Chs2. Here, we report that Dbf2, a conserved mitotic exit kinase, localizes to the division site after Chs2 and directly phosphorylates Chs2 on several residues, including Ser-217. Both phosphodeficient (chs2‑S217A) and phosphomimic (chs2‑S217D) mutations cause defects in cytokinesis, suggesting that dynamic phosphorylation–dephosphorylation of Ser-217 is critical for Chs2 function. It is striking that Chs2‑S217A constricts asymmetrically with the actomyosin ring (AMR), whereas Chs2-S217D displays little or no constriction and remains highly mobile at the division site. These data suggest that Chs2 phosphorylation by Dbf2 triggers its dissociation from the AMR during the late stage of cytokinesis. Of interest, both chs2‑S217A and chs2‑S217D mutants are robustly suppressed by increased dosage of Cyk3, a cytokinesis protein that displays Dbf2‑dependent localization and also stimulates Chs2‑mediated chitin synthesis. Thus Dbf2 regulates PS formation through at least two independent pathways: direct phosphorylation and Cyk3‑mediated activation of Chs2. Our study establishes a mechanism for direct cell cycle control of ECM remodeling during cytokinesis.

scholarly journals Computational modelling of mitotic exit in budding yeast: the role of separase and Cdc14 endocycles

2011 ◽  
Vol 8 (61) ◽  
pp. 1128-1141 ◽  
Author(s):  
P. K. Vinod ◽  
Paula Freire ◽  
Ahmed Rattani ◽  
Andrea Ciliberto ◽  
Frank Uhlmann ◽  
...  
Keyword(s):  
Regulatory Networks ◽  
Budding Yeast ◽  
Cell Cycle Control ◽  
Computational Modelling ◽  
Eukaryotic Cell ◽  
Mitotic Exit ◽  
Intuitive Reasoning ◽  
Systematic Analysis ◽  
Systems View

The operating principles of complex regulatory networks are best understood with the help of mathematical modelling rather than by intuitive reasoning. Hereby, we study the dynamics of the mitotic exit (ME) control system in budding yeast by further developing the Queralt's model. A comprehensive systems view of the network regulating ME is provided based on classical experiments in the literature. In this picture, Cdc20–APC is a critical node controlling both cyclin (Clb2 and Clb5) and phosphatase (Cdc14) branches of the regulatory network. On the basis of experimental situations ranging from single to quintuple mutants, the kinetic parameters of the network are estimated. Numerical analysis of the model quantifies the dependence of ME control on the proteolytic and non-proteolytic functions of separase. We show that the requirement of the non-proteolytic function of separase for ME depends on cyclin-dependent kinase activity. The model is also used for the systematic analysis of the recently discovered Cdc14 endocycles. The significance of Cdc14 endocycles in eukaryotic cell cycle control is discussed as well.

scholarly journals The role of FBXW7, a cell-cycle regulator, as a predictive marker of recurrence of gastrointestinal stromal tumors

2019 ◽  
Vol 22 (6) ◽  
pp. 1100-1108
Author(s):  
Yuki Koga ◽  
Masaaki Iwatsuki ◽  
Kohei Yamashita ◽  
Yuki Kiyozumi ◽  
Junji Kurashige ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Gastrointestinal Stromal Tumors ◽  
Predictive Marker ◽  
Stromal Tumors ◽  
Cell Cycle Regulator ◽  
A Cell

scholarly journals Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae

2009 ◽  
Vol 185 (6) ◽  
pp. 995-1012 ◽  
Author(s):  
Ryuichi Nishihama ◽  
Jennifer H. Schreiter ◽  
Masayuki Onishi ◽  
Elizabeth A. Vallen ◽  
Julia Hanna ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mitotic Exit ◽  
Chitin Synthase ◽  
Cleavage Furrow ◽  
Sh3 Domains ◽  
C2 Domains ◽  
Division Site ◽  
Primary Septum ◽  
N Terminus

Cytokinesis requires coordination of actomyosin ring (AMR) contraction with rearrangements of the plasma membrane and extracellular matrix. In Saccharomyces cerevisiae, new membrane, the chitin synthase Chs2 (which forms the primary septum [PS]), and the protein Inn1 are all delivered to the division site upon mitotic exit even when the AMR is absent. Inn1 is essential for PS formation but not for Chs2 localization. The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Δ cells). The Inn1 N terminus resembles C2 domains but does not appear to bind phospholipids; nonetheless, when overexpressed or fused to Hof1, it can provide Inn1 function even in the absence of the AMR. Thus, Inn1 and Cyk3 appear to cooperate in activating Chs2 for PS formation, which allows coordination of AMR contraction with ingression of the cleavage furrow.

scholarly journals Ras/cAMP-dependent Protein Kinase (PKA) Regulates Multiple Aspects of Cellular Events by Phosphorylating the Whi3 Cell Cycle Regulator in Budding Yeast

2013 ◽  
Vol 288 (15) ◽  
pp. 10558-10566 ◽  
Author(s):  
Masaki Mizunuma ◽  
Ryohei Tsubakiyama ◽  
Takafumi Ogawa ◽  
Atsunori Shitamukai ◽  
Yoshifumi Kobayashi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Budding Yeast ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Cellular Events ◽  
Cell Cycle Regulator ◽  
Dependent Protein

Proteomic Analysis of Acute Promyelocytic Leukemia Reveals That PML-RARalpha Induces Cell Cycle Progression and Mitotic Exit by Increased Expression and Decreased Ser63 Phosphorylation of OP18.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2028-2028
Author(s):  
A. PeerZada ◽  
M. Geletu ◽  
J. Pullikan ◽  
V. Reddy ◽  
W. Hiddemann ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Acute Promyelocytic Leukemia ◽  
Cell Cycle Progression ◽  
Promyelocytic Leukemia ◽  
Mitotic Exit ◽  
Cycle Progression ◽  
2D Gel ◽  
First Time ◽  
Common Cell

Abstract We applied a mass spectrometry based approach to explore the proteins differentially regulated by PML-RARalpha, a translocation characteristic of acute promyelocytic leukemia (APL). Bioinformatic pathway analysis placed the 46 identified PML-RARalpha regulated proteins into three major networks, OP18-MAPK1, HSP-STAT3 and CCT-MYC. Using this approach, we were able to generate a common cell cycle network of the proteins in these pathways. Further analysis indicated that mRNA expression of OP18, which belonged to this network, was elevated in APL patients and the increased OP18 protein expression upon PML-RARalpha induction was overcome by retinoic acid treatment. Here we also report, for the first time a novel role of PML-RARalpha in cell cycle progression and mitotic exit. RNA interference experiments revealed that siRNA against OP18 overcomes PML-RARalpha effects on cell cycle progression. In addition to increased OP18 expression by PML-RARalpha, 2D gel electrophoresis revealed an isomer of OP18, subsequently confirmed by 2D-western as ser63 phosphomer to be downregulated by PML-RARalpha. Based on these findings, point mutation experiments indicated that decreased phosphorylation of ser63 in OP18 is important for PML-RARalpha mediated cell cycle and mitotic index effects since a constitutive phosphorylated mutant (ser63/asp) of OP18 overcame the PML-RARalpha effects in U9/PR cells, NB4 and APL patients. In summary, our results demonstrate that the effect of PML-RARalpha on cell cycle progression and mitotic exit is via two mechanisms: increasing the expression of OP18 and decreasing the phosphorylation of OP18 at ser63.

scholarly journals Budding Yeast Bub2 Is Localized at Spindle Pole Bodies and Activates the Mitotic Checkpoint via a Different Pathway from Mad2

1999 ◽  
Vol 145 (5) ◽  
pp. 979-991 ◽  
Author(s):  
Roberta Fraschini ◽  
Elisa Formenti ◽  
Giovanna Lucchini ◽  
Simonetta Piatti
Keyword(s):  
Cell Cycle ◽  
Mitotic Spindle ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Spindle Pole Body ◽  
Mitotic Checkpoint ◽  
Spindle Pole ◽  
Cycle Progression ◽  
Spindle Pole Bodies

The mitotic checkpoint blocks cell cycle progression before anaphase in case of mistakes in the alignment of chromosomes on the mitotic spindle. In budding yeast, the Mad1, 2, 3, and Bub1, 2, 3 proteins mediate this arrest. Vertebrate homologues of Mad1, 2, 3, and Bub1, 3 bind to unattached kinetochores and prevent progression through mitosis by inhibiting Cdc20/APC-mediated proteolysis of anaphase inhibitors, like Pds1 and B-type cyclins. We investigated the role of Bub2 in budding yeast mitotic checkpoint. The following observations indicate that Bub2 and Mad1, 2 probably activate the checkpoint via different pathways: (a) unlike the other Mad and Bub proteins, Bub2 localizes at the spindle pole body (SPB) throughout the cell cycle; (b) the effect of concomitant lack of Mad1 or Mad2 and Bub2 is additive, since nocodazole-treated mad1 bub2 and mad2 bub2 double mutants rereplicate DNA more rapidly and efficiently than either single mutant; (c) cell cycle progression of bub2 cells in the presence of nocodazole requires the Cdc26 APC subunit, which, conversely, is not required for mad2 cells in the same conditions. Altogether, our data suggest that activation of the mitotic checkpoint blocks progression through mitosis by independent and partially redundant mechanisms.

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