scholarly journals Spindle Position Is Coordinated with Cell-Cycle Progression through Establishment of Mitotic Exit-Activating and -Inhibitory Zones

2010 ◽  
Vol 39 (3) ◽  
pp. 444-454 ◽  
Author(s):  
Leon Y. Chan ◽  
Angelika Amon
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Mitotic Exit ◽  
Cycle Progression ◽  
Spindle Position

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 Elm1 kinase activates the spindle position checkpoint kinase Kin4

2010 ◽  
Vol 190 (6) ◽  
pp. 975-989 ◽  
Author(s):  
Ayse Koca Caydasi ◽  
Bahtiyar Kurtulmus ◽  
Maria I.L. Orrico ◽  
Astrid Hofmann ◽  
Bashar Ibrahim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Kinase Activity ◽  
Asymmetric Cell Division ◽  
Cycle Progression ◽  
Spindle Positioning ◽  
Surveillance Mechanism ◽  
Spindle Position ◽  
Conserved Residue

Budding yeast asymmetric cell division relies upon the precise coordination of spindle orientation and cell cycle progression. The spindle position checkpoint (SPOC) is a surveillance mechanism that prevents cells with misoriented spindles from exiting mitosis. The cortical kinase Kin4 acts near the top of this network. How Kin4 kinase activity is regulated and maintained in respect to spindle positional cues remains to be established. Here, we show that the bud neck–associated kinase Elm1 participates in Kin4 activation and SPOC signaling by phosphorylating a conserved residue within the activation loop of Kin4. Blocking Elm1 function abolishes Kin4 kinase activity in vivo and eliminates the SPOC response to spindle misalignment. These findings establish a novel function for Elm1 in the coordination of spindle positioning with cell cycle progression via its control of Kin4.

scholarly journals Human cells lacking CDC14A and CDC14B show differences in ciliogenesis but not in mitotic progression

2020 ◽  
pp. jcs.255950
Author(s):  
Patrick Partscht ◽  
Borhan Uddin ◽  
Elmar Schiebel
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Mitotic Exit ◽  
Human Cells ◽  
Mitotic Progression ◽  
Cycle Progression ◽  
Double Deletion ◽  
Redundant Functions

Budding yeast Cdc14 phosphatase has a central role in mitotic exit and cytokinesis. Puzzlingly, a uniform picture for the three human CDC14 paralogues hCDC14A, B and C in cell cycle control has not emerged to date. Redundant functions between the three hCDC14 phosphatases could explain this unclear picture. To address the possibility of redundancy, we tested expression of hCDC14 and analysed cell cycle progression of cells with single- and double-deletion in hCDC14 genes. Our data suggest that hCDC14C is not expressed in human RPE1 cells excluding a function in this cell line. Single- and double-knockouts (KO) of hCDC14A and hCDC14B in RPE1 cells indicate that both phosphatases are not important for the timing of mitotic phases, cytokinesis and cell proliferation. However, cycling hCDC14A KO and hCDC14B KO cells show altered ciliogenesis compared to WT cells. The cilia of cycling hCDC14A KO cells are longer, whereas hCDC14B KO cilia are more frequent and disassemble faster. In conclusion, this study demonstrates that the cell cycle functions of CDC14 proteins are not conserved between yeast and human cells.

scholarly journals The Mitotic Cyclins Clb2p and Clb4p Affect Morphogenesis inCandida albicans

2005 ◽  
Vol 16 (7) ◽  
pp. 3387-3400 ◽  
Author(s):  
Eric S. Bensen ◽  
Andres Clemente-Blanco ◽  
Kenneth R. Finley ◽  
Jaime Correa-Bordes ◽  
Judith Berman
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Filamentous Growth ◽  
Mitotic Exit ◽  
Cycle Progression ◽  
Yeast Form ◽  
Cell Cycle Machinery ◽  
Incandida Albicans

The ability of Candida albicans to switch cellular morphologies is crucial for its ability to cause infection. Because the cell cycle machinery participates in Saccharomyces cerevisiae filamentous growth, we characterized in detail the two C. albicans B-type cyclins, CLB2 and CLB4, to better understand the molecular mechanisms that underlie the C. albicans morphogenic switch. Both Clb2p and Clb4p levels are cell cycle regulated, peaking at G2/M and declining before mitotic exit. On hyphal induction, the accumulation of the G1 cyclin Cln1p was prolonged, whereas the accumulation of both Clb proteins was delayed when compared with yeast form cells, indicating that CLB2 and CLB4 are differentially regulated in the two morphologies and that the dynamics of cyclin appearance differs between yeast and hyphal forms of growth. Clb2p-depleted cells were inviable and arrested with hyper-elongated projections containing two nuclei, suggesting that Clb2p is not required for entry into mitosis. Unlike Clb2p-depleted cells, Clb4p-depleted cells were viable and formed constitutive pseudohyphae. Clb proteins lacking destruction box domains blocked cell cycle progression resulting in the formation of long projections, indicating that both Clb2p and Clb4p must be degraded before mitotic exit. In addition, overexpression of either B-type cyclin reduced the extent of filamentous growth. Taken together, these data indicate that Clb2p and Clb4p regulate C. albicans morphogenesis by negatively regulating polarized growth.

scholarly journals Hog1 activation delays mitotic exit via phosphorylation of Net1

2020 ◽  
Vol 117 (16) ◽  
pp. 8924-8933
Author(s):  
Silvia Tognetti ◽  
Javier Jiménez ◽  
Matteo Viganò ◽  
Alba Duch ◽  
Ethel Queralt ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Survival ◽  
Cell Cycle Progression ◽  
Environmental Changes ◽  
Genome Instability ◽  
Mitotic Exit ◽  
Cycle Progression ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
Promote Cell Survival

Adaptation to environmental changes is crucial for cell fitness. In Saccharomyces cerevisiae, variations in external osmolarity trigger the activation of the stress-activated protein kinase Hog1 (high-osmolarity glycerol 1), which regulates gene expression, metabolism, and cell-cycle progression. The activation of this kinase leads to the regulation of G1, S, and G2 phases of the cell cycle to prevent genome instability and promote cell survival. Here we show that Hog1 delays mitotic exit when cells are stressed during metaphase. Hog1 phosphorylates the nucleolar protein Net1, altering its affinity for the phosphatase Cdc14, whose activity is essential for mitotic exit and completion of the cell cycle. The untimely release of Cdc14 from the nucleolus upon activation of Hog1 is linked to a defect in ribosomal DNA (rDNA) and telomere segregation, and it ultimately delays cell division. A mutant of Net1 that cannot be phosphorylated by Hog1 displays reduced viability upon osmostress. Thus, Hog1 contributes to maximizing cell survival upon stress by regulating mitotic exit.

scholarly journals DNA Damage Checkpoints Inhibit Mitotic Exit by Two Different Mechanisms

2007 ◽  
Vol 27 (14) ◽  
pp. 5067-5078 ◽  
Author(s):  
Fengshan Liang ◽  
Yanchang Wang
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Mitotic Exit ◽  
Yeast Cells ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Dna Damage Checkpoints ◽  
Early Anaphase

ABSTRACT Cyclin-dependent kinase (CDK) governs cell cycle progression, and its kinase activity fluctuates during the cell cycle. Mitotic exit pathways are responsible for the inactivation of CDK after chromosome segregation by promoting the release of a nucleolus-sequestered phosphatase, Cdc14, which antagonizes CDK. In the budding yeast Saccharomyces cerevisiae, mitotic exit is controlled by the FEAR (for “Cdc-fourteen early anaphase release”) and mitotic exit network (MEN) pathways. In response to DNA damage, two branches of the DNA damage checkpoint, Chk1 and Rad53, are activated in budding yeast to prevent anaphase entry and mitotic exit, allowing cells more time to repair damaged DNA. Here we present evidence indicating that yeast cells negatively regulate mitotic exit through two distinct pathways in response to DNA damage. Rad53 prevents mitotic exit by inhibiting the MEN pathway, whereas the Chk1 pathway prevents FEAR pathway-dependent Cdc14 release in the presence of DNA damage. In contrast to previous data, the Rad53 pathway negatively regulates MEN independently of Cdc5, a Polo-like kinase essential for mitotic exit. Instead, a defective Rad53 pathway alleviates the inhibition of MEN by Bfa1.

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