scholarly journals SUMOylation stabilizes sister kinetochore biorientation to allow timely anaphase

2021 ◽  
Vol 220 (7) ◽  
Author(s):  
Xue Bessie Su ◽  
Menglu Wang ◽  
Claudia Schaffner ◽  
Olga O. Nerusheva ◽  
Dean Clift ◽  
...  
Keyword(s):  
Error Correction ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Sister Kinetochore ◽  
Phosphatase 2A ◽  
Chromosome Passenger Complex

During mitosis, sister chromatids attach to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension, which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore–microtubule attachments remains unclear. Here we show that SUMOylation dampens error correction to allow stable sister kinetochore biorientation and timely anaphase onset. The Siz1/Siz2 SUMO ligases modify the pericentromere-localized shugoshin (Sgo1) protein before its tension-dependent release from chromatin. Sgo1 SUMOylation reduces its binding to protein phosphatase 2A (PP2A), and weakening of this interaction is important for stable biorientation. Unstable biorientation in SUMO-deficient cells is associated with persistence of the chromosome passenger complex (CPC) at centromeres, and SUMOylation of CPC subunit Bir1 also contributes to timely anaphase onset. We propose that SUMOylation acts in a combinatorial manner to facilitate dismantling of the error correction machinery within pericentromeres and thereby sharpen the metaphase–anaphase transition.

scholarly journals SUMOylation targets shugoshin to stabilize sister kinetochore biorientation

2019 ◽  
Author(s):  
Xue Bessie Su ◽  
Menglu Wang ◽  
Claudia Schaffner ◽  
Dean Clift ◽  
Olga O. Nerusheva ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Aurora B ◽  
Cycle Progression ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Sister Kinetochore ◽  
Phosphatase 2A ◽  
Segregation Of Chromosomes

AbstractThe accurate segregation of chromosomes during mitosis relies on the attachment of sister chromatids to microtubules from opposite poles, called biorientation. Sister chromatid cohesion resists microtubule forces, generating tension which provides the signal that biorientation has occurred. How tension silences the surveillance pathways that prevent cell cycle progression and correct erroneous kinetochore-microtubule remains unclear. Here we identify SUMOylation as a mechanism that promotes anaphase onset upon biorientation. SUMO ligases modify the tension-sensing pericentromere-localized chromatin protein, shugoshin, to stabilize bioriented sister kinetochore-microtubule attachments. In the absence of SUMOylation, Aurora B kinase removal from kinetochores is delayed. Shugoshin SUMOylation prevents its binding to protein phosphatase 2A (PP2A) and release of this interaction is important for stabilizing sister kinetochore biorientation. We propose that SUMOylation modulates the kinase-phosphatase balance within pericentromeres to inactivate the error correction machinery, thereby allowing anaphase entry in response to biorientation.

Identification of a protein phosphatase 2A family member that regulates cell cycle progression in Trypanosoma brucei

2014 ◽  
Vol 194 (1-2) ◽  
pp. 48-52 ◽  
Author(s):  
Karen G. Rothberg ◽  
Neal Jetton ◽  
James G. Hubbard ◽  
Daniel A. Powell ◽  
Vidya Pandarinath ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Family Member ◽  
Trypanosoma Brucei ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Cycle Progression ◽  
Phosphatase 2A

scholarly journals Cdc55 coordinates spindle assembly and chromosome disjunction during meiosis

2011 ◽  
Vol 193 (7) ◽  
pp. 1213-1228 ◽  
Author(s):  
Farid Bizzari ◽  
Adele L. Marston
Keyword(s):  
Protein Phosphatase ◽  
Deoxyribonucleic Acid ◽  
Nuclear Division ◽  
Spindle Assembly ◽  
Regulatory Subunit ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Phosphatase 2A ◽  
Meiosis I ◽  
Sequential Assembly

During meiosis, two consecutive nuclear divisions follow a single round of deoxyribonucleic acid replication. In meiosis I, homologues are segregated, whereas in meiosis II, sister chromatids are segregated. This requires that the sequential assembly and dissolution of specialized chromosomal factors are coordinated with two rounds of spindle assembly and disassembly. How these events are coupled is unknown. In this paper, we show, in budding yeast, that the protein phosphatase 2A regulatory subunit Cdc55 couples the loss of linkages between chromosomes with nuclear division by restraining two other phosphatases, Cdc14 and PP2ARts1. Cdc55 maintains Cdc14 sequestration in the nucleolus during early meiosis, and this is essential for the assembly of the meiosis I spindle but not for chromosomes to separate. Cdc55 also limits the formation of PP2A holocomplexes containing the alternative regulatory subunit Rts1, which is crucial for the timely dissolution of sister chromatid cohesion. Therefore, Cdc55 orders passage through the meiotic divisions by ensuring a balance of phosphatases.

scholarly journals The budding yeast PP2ACdc55 protein phosphatase prevents the onset of anaphase in response to morphogenetic defects

2007 ◽  
Vol 177 (4) ◽  
pp. 599-611 ◽  
Author(s):  
Elena Chiroli ◽  
Valentina Rossio ◽  
Giovanna Lucchini ◽  
Simonetta Piatti
Keyword(s):  
Protein Phosphatase ◽  
Budding Yeast ◽  
S Phase ◽  
Yeast Cells ◽  
Regulatory Subunit ◽  
Chromosome Transmission ◽  
Anaphase Onset ◽  
Sister Chromatids ◽  
Chromatid Cohesion ◽  
Noncanonical Pathway

Faithful chromosome transmission requires establishment of sister chromatid cohesion during S phase, followed by its removal at anaphase onset. Sister chromatids are tethered together by cohesin, which is displaced from chromosomes through cleavage of its Mcd1 subunit by the separase protease. Separase is in turn inhibited, up to this moment, by securin. Budding yeast cells respond to morphogenetic defects by a transient arrest in G2 with high securin levels and unseparated chromatids. We show that neither securin elimination nor forced cohesin cleavage is sufficient for anaphase in these conditions, suggesting that other factors contribute to cohesion maintainance in G2. We find that the protein phosphatase PP2A bound to its regulatory subunit Cdc55 plays a key role in this process, uncovering a new function for PP2ACdc55 in controlling a noncanonical pathway of chromatid cohesion removal.

scholarly journals Signaling from Polyomavirus Middle T and Small T Defines Different Roles for Protein Phosphatase 2A

1998 ◽  
Vol 18 (12) ◽  
pp. 7556-7564 ◽  
Author(s):  
Karen P. Mullane ◽  
Mara Ratnofsky ◽  
Xavier Culleré ◽  
Brian Schaffhausen
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
T Antigen ◽  
Functional Difference ◽  
Cycle Progression ◽  
Jun Kinase ◽  
Phosphatase 2A ◽  
Promote Cell Cycle Progression

ABSTRACT Polyomavirus causes a broad spectrum of tumors as the result of the action of its early proteins. This work compares signaling from middle T antigen (MT), the major transforming protein, to that from small T antigen (ST). The abilities of MT mutants to promote cell cycle progression in serum-starved NIH 3T3 cells were compared. Transformation-defective mutants lacking association with SHC or with phosphatidylinositol 3-kinase (PI3-K) retained the ability to induce DNA synthesis as measured by bromodeoxyuridine incorporation. Only when both interactions were lost in the Y250F/Y315F double mutant was MT inactive. ST promoted cell cycle progression in a manner dependent on its binding of protein phosphatase 2A (PP2A). Since the Y250F/Y315F MT mutant was wild type for PP2A binding yet unable to promote cell cycle progression, while ST was capable of promoting cell cycle progression, these experiments revealed a functional difference in MT and ST signaling via PP2A. Assays testing the abilities of MT and ST to induce the c-fos promoter and to activate c-jun kinase led to the same conclusion. ST, but not Y250F/Y315F MT, was able to activate the c-fos promoter through its interaction with PP2A. In contrast, MT, but not ST, was able to activate c-jun kinase by virtue of its interaction with PP2A.

scholarly journals Regulation of the Cell Cycle by Protein Phosphatase 2A in Saccharomyces cerevisiae

2006 ◽  
Vol 70 (2) ◽  
pp. 440-449 ◽  
Author(s):  
Yu Jiang
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Cycle ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Phosphatase 2A ◽  
Direct Target ◽  
Cycle Regulation

SUMMARY Protein phosphatase 2A (PP2A) has long been implicated in cell cycle regulation in many different organisms. In the yeast Saccharomyces cerevisiae, PP2A controls cell cycle progression mainly through modulation of cyclin-dependent kinase (CDK) at the G2/M transition. However, CDK does not appear to be a direct target of PP2A. PP2A affects CDK activity through its roles in checkpoint controls. Inactivation of PP2A downregulates CDK by activating the morphogenesis checkpoint and, consequently, delays mitotic entry. Defects in PP2A also compromise the spindle checkpoint and predispose the cell to an error-prone mitotic exit. In addition, PP2A is involved in controlling the G1/S transition and cytokinesis. These findings suggest that PP2A functions in many stages of the cell cycle and its effect on cell cycle progression is pleiotropic.

scholarly journals Regulation of Mih1/Cdc25 by protein phosphatase 2A and casein kinase 1

2008 ◽  
Vol 180 (5) ◽  
pp. 931-945 ◽  
Author(s):  
Gayatri Pal ◽  
Maria T.Z. Paraz ◽  
Douglas R. Kellogg
Keyword(s):  
Cell Cycle ◽  
Protein Phosphatase ◽  
Feedback Loop ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Casein Kinase ◽  
Cycle Progression ◽  
Signaling Mechanism ◽  
Casein Kinase 1 ◽  
Phosphatase 2A

The Cdc25 phosphatase promotes entry into mitosis by removing cyclin-dependent kinase 1 (Cdk1) inhibitory phosphorylation. Previous work suggested that Cdc25 is activated by Cdk1 in a positive feedback loop promoting entry into mitosis; however, it has remained unclear how the feedback loop is initiated. To learn more about the mechanisms that regulate entry into mitosis, we have characterized the function and regulation of Mih1, the budding yeast homologue of Cdc25. We found that Mih1 is hyperphosphorylated early in the cell cycle and is dephosphorylated as cells enter mitosis. Casein kinase 1 is responsible for most of the hyperphosphorylation of Mih1, whereas protein phosphatase 2A associated with Cdc55 dephosphorylates Mih1. Cdk1 appears to directly phosphorylate Mih1 and is required for initiation of Mih1 dephosphorylation as cells enter mitosis. Collectively, these observations suggest that Mih1 regulation is achieved by a balance of opposing kinase and phosphatase activities. Because casein kinase 1 is associated with sites of polar growth, it may regulate Mih1 as part of a signaling mechanism that links successful completion of growth-related events to cell cycle progression.

scholarly journals Protein phosphatase 2A is expressed in response to colony-stimulating factor 1 in macrophages and is required for cell cycle progression independently of extracellular signal-regulated protein kinase activity

1999 ◽  
Vol 339 (3) ◽  
pp. 517-524 ◽  
Author(s):  
Nicholas J. WILSON ◽  
Suzanne T. MOSS ◽  
Xavier F. CSAR ◽  
Alister C. WARD ◽  
John A. HAMILTON
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Protein Phosphatase ◽  
Cell Cycle Progression ◽  
Protein Phosphatase 2A ◽  
Colony Stimulating Factor ◽  
Cycle Progression ◽  
Extracellular Signal ◽  
Phosphatase 2A ◽  
Stimulating Factor

Colony-stimulating factor 1 (CSF-1) is required for the development of monocytes/macrophages from progenitor cells and for the survival and activation of mature macrophages. The receptor for CSF-1 is the product of the c-fms proto-oncogene, which, on binding ligand, can stimulate a mitogenic response in the appropriate cells. To investigate which genes are regulated in response to CSF-1-stimulation in murine bone-marrow-derived macrophages (BMM), we employed mRNA differential display reverse transcriptase-mediated PCR to identify cDNA species induced by CSF-1. Both Northern and Western blot analyses confirmed the increased expression of one of the cDNA species identified as coding for the catalytic subunit of protein phosphatase 2A (PP2A), an observation not previously reported during the response to a growth factor. To determine the significance of the increased expression of PP2A in response to CSF-1, the PP2A inhibitor okadaic acid (OA) was added to CSF-1-treated BMM and found to inhibit DNA synthesis in a dose-dependent manner. Further analysis with flow cytometry in the presence of OA led to the novel conclusion that PP2A activity is critical for CSF-1-driven BMM cell cycle progression in both early G1 and S phases. Surprisingly, in the light of previous studies with other cells, the PP2A-dependent proliferation could be dissociated from activation by extracellular signal-regulated protein kinase (ERK) in macrophages because OA did not affect either the basal or CSF-1-induced ERK activity in BMM. Two-dimensional SDS/PAGE analysis of lysates of 32P-labelled BMM, which had been treated with CSF-1 in the presence or absence of OA, identified candidate substrates for PP2A.

scholarly journals Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression

2017 ◽  
Vol 114 (37) ◽  
pp. 9906-9911 ◽  
Author(s):  
Reem M. Alomer ◽  
Eulália M. L. da Silva ◽  
Jingrong Chen ◽  
Katarzyna M. Piekarz ◽  
Katherine McDonald ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Cell Cycle Progression ◽  
Loop Formation ◽  
Cycle Progression ◽  
Sister Chromatids ◽  
Dependent Inactivation ◽  
Chromatid Cohesion ◽  
N Terminus ◽  
Dependent Modification ◽  
Unique Ability

Sister chromatids are tethered together by the cohesin complex from the time they are made until their separation at anaphase. The ability of cohesin to tether sister chromatids together depends on acetylation of its Smc3 subunit by members of the Eco1 family of cohesin acetyltransferases. Vertebrates express two orthologs of Eco1, called Esco1 and Esco2, both of which are capable of modifying Smc3, but their relative contributions to sister chromatid cohesion are unknown. We therefore set out to determine the precise contributions of Esco1 and Esco2 to cohesion in vertebrate cells. Here we show that cohesion establishment is critically dependent upon Esco2. Although most Smc3 acetylation is Esco1 dependent, inactivation of the ESCO1 gene has little effect on mitotic cohesion. The unique ability of Esco2 to promote cohesion is mediated by sequences in the N terminus of the protein. We propose that Esco1-dependent modification of Smc3 regulates almost exclusively the noncohesive activities of cohesin, such as DNA repair, transcriptional control, chromosome loop formation, and/or stabilization. Collectively, our data indicate that Esco1 and Esco2 contribute to distinct and separable activities of cohesin in vertebrate cells.

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