scholarly journals Protein phosphatases in the regulation of mitosis

2018 ◽  
Vol 218 (2) ◽  
pp. 395-409 ◽  
Author(s):  
Jakob Nilsson
Keyword(s):  
Protein Function ◽  
Proper Time ◽  
Protein Phosphatases ◽  
Genetic Material ◽  
Substrate Selection ◽  
Animal Cells ◽  
Mitotic Kinases ◽  
Daughter Cells ◽  
Phosphoprotein Phosphatases ◽  
Binding Cleft

The accurate segregation of genetic material to daughter cells during mitosis depends on the precise coordination and regulation of hundreds of proteins by dynamic phosphorylation. Mitotic kinases are major regulators of protein function, but equally important are protein phosphatases that balance their actions, their coordinated activity being essential for accurate chromosome segregation. Phosphoprotein phosphatases (PPPs) that dephosphorylate phosphoserine and phosphothreonine residues are increasingly understood as essential regulators of mitosis. In contrast to kinases, the lack of a pronounced peptide-binding cleft on the catalytic subunit of PPPs suggests that these enzymes are unlikely to be specific. However, recent exciting insights into how mitotic PPPs recognize specific substrates have revealed that they are as specific as kinases. Furthermore, the activities of PPPs are tightly controlled at many levels to ensure that they are active only at the proper time and place. Here, I will discuss substrate selection and regulation of mitotic PPPs focusing mainly on animal cells and explore how these actions control mitosis, as well as important unanswered questions.

Specificity determinants of phosphoprotein phosphatases controlling kinetochore functions

2020 ◽  
Vol 64 (2) ◽  
pp. 325-336 ◽  
Author(s):  
Dimitriya H. Garvanska ◽  
Jakob Nilsson
Keyword(s):  
Spindle Assembly Checkpoint ◽  
Activity Level ◽  
Phosphorylation Sites ◽  
Binding Affinities ◽  
Mitotic Kinases ◽  
Anaphase Onset ◽  
Phosphoprotein Phosphatases ◽  
Linear Motifs ◽  
Temporal And Spatial ◽  
Kinetochore Function

Abstract Kinetochores are instrumental for accurate chromosome segregation by binding to microtubules in order to move chromosomes and by delaying anaphase onset through the spindle assembly checkpoint (SAC). Dynamic phosphorylation of kinetochore components is key to control these activities and is tightly regulated by temporal and spatial recruitment of kinases and phosphoprotein phosphatases (PPPs). Here we focus on PP1, PP2A-B56 and PP2A-B55, three PPPs that are important regulators of mitosis. Despite the fact that these PPPs share a very similar active site, they target unique ser/thr phosphorylation sites to control kinetochore function. Specificity is in part achieved by PPPs binding to short linear motifs (SLiMs) that guide their substrate specificity. SLiMs bind to conserved pockets on PPPs and are degenerate in nature, giving rise to a range of binding affinities. These SLiMs control the assembly of numerous substrate specifying complexes and their position and binding strength allow PPPs to target specific phosphorylation sites. In addition, the activity of PPPs is regulated by mitotic kinases and inhibitors, either directly at the activity level or through affecting PPP–SLiM interactions. Here, we discuss recent progress in understanding the regulation of PPP specificity and activity and how this controls kinetochore biology.

scholarly journals Dem Anfang auf der Spur — die Suche nach DNA-Replikationsursprüngen

BIOspektrum ◽  
2021 ◽  
Vol 27 (3) ◽  
pp. 246-249
Author(s):  
Elisabeth Kruse ◽  
Stephan Hamperl
Keyword(s):  
Cell Division ◽  
Dna Synthesis ◽  
Genomic Dna ◽  
Genetic Material ◽  
Uniform Method ◽  
Replication Origins ◽  
Daughter Cells ◽  
Origins Of Replication ◽  
Mammalian Genomes ◽  
Comprehensive Manner

AbstractTimely and accurate duplication of DNA prior to cell division is a prerequisite for propagation of the genetic material to both daughter cells. DNA synthesis initiates at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, a uniform method that identifies origins of replication in a comprehensive manner is still missing. Here, we present currently available and discuss new approaches to map replication origins in mammalian genomes.

Identification, purification, and characterization of phosphotyrosine-specific protein phosphatases from cultured chicken embryo fibroblasts

1984 ◽  
Vol 4 (6) ◽  
pp. 1003-1012
Author(s):  
R L Nelson ◽  
P E Branton
Keyword(s):  
Chicken Embryo ◽  
Protein Phosphatases ◽  
Gel Filtration ◽  
Deae Cellulose ◽  
Soluble Form ◽  
Ph Optimum ◽  
Cell Extracts ◽  
Phosphoprotein Phosphatases ◽  
Embryo Fibroblasts ◽  
Chicken Embryo Fibroblasts

Tyrosine phosphorylation catalyzed by a unique class of protein kinases is an important process in both normal cell proliferation and oncogenic transformation. In this study, phosphoprotein phosphatases specific for the dephosphorylation of phosphotyrosine residues were partially purified from secondary chicken embryo fibroblasts, using 32P-labeled immunoglobulin G phosphorylated by pp60src as substrate. Crude cell extracts contained ca. 70% of the activity in the soluble form and ca. 30% associated with a crude membrane fraction. The soluble activity was purified by using DEAE-cellulose and carboxymethyl cellulose column chromatography and gel filtration, and at least three enzyme species of apparent Mr 55,000 (pTPI), 50,000 (pTPII), and 95,000 (pTPIII)--comprising ca. 20, 45, and 35%, respectively, of the total activity--were resolved. All three enzymes possessed somewhat similar properties. They had a pH optimum of about 7.4, they were inhibited by Zn2+, vanadate, ATP, and ADP, and they were unaffected by divalent metal cations, EDTA, and F- under standard assay conditions employing a physiological ionic strength. These properties suggest that they represent a class of enzymes distinct from well-known phosphoseryl-phosphothreonyl-protein phosphatases and that dephosphorylation of phosphotyrosine-containing proteins may be carried out by a unique family of phosphoprotein phosphatases. Transformation by Rous sarcoma virus resulted in a small increase in phosphotyrosyl-protein phosphatase activity.

scholarly journals Cell Cycle and DNA Repair Regulation in the Damage Response: Protein Phosphatases Take Over the Reins

2020 ◽  
Vol 21 (2) ◽  
pp. 446 ◽  
Author(s):  
Adrián Campos ◽  
Andrés Clemente-Blanco
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cellular Response ◽  
Molecular Mechanisms ◽  
Protein Phosphatases ◽  
Genetic Material ◽  
Protein Composition ◽  
Genotoxic Stress ◽  
Damage Response ◽  
Protein Dephosphorylation

Cells are constantly suffering genotoxic stresses that affect the integrity of our genetic material. Genotoxic insults must be repaired to avoid the loss or inappropriate transmission of the genetic information, a situation that could lead to the appearance of developmental abnormalities and tumorigenesis. To combat this threat, eukaryotic cells have evolved a set of sophisticated molecular mechanisms that are collectively known as the DNA damage response (DDR). This surveillance system controls several aspects of the cellular response, including the detection of lesions, a temporary cell cycle arrest, and the repair of the broken DNA. While the regulation of the DDR by numerous kinases has been well documented over the last decade, the complex roles of protein dephosphorylation have only recently begun to be investigated. Here, we review recent progress in the characterization of DDR-related protein phosphatases during the response to a DNA lesion, focusing mainly on their ability to modulate the DNA damage checkpoint and the repair of the damaged DNA. We also discuss their protein composition and structure, target specificity, and biochemical regulation along the different stages encompassed in the DDR. The compilation of this information will allow us to better comprehend the physiological significance of protein dephosphorylation in the maintenance of genome integrity and cell viability in response to genotoxic stress.

scholarly journals How cortical waves drive fission of motile cells

2020 ◽  
Vol 117 (12) ◽  
pp. 6330-6338 ◽  
Author(s):  
Sven Flemming ◽  
Francesc Font ◽  
Sergio Alonso ◽  
Carsten Beta
Keyword(s):  
Reaction Diffusion ◽  
Cortical Actin ◽  
Animal Cells ◽  
Contractile Ring ◽  
Daughter Cells ◽  
Reaction Diffusion Model ◽  
Motile Cells ◽  
A Cell ◽  
Actin Waves ◽  
Cell Growth And Proliferation

Cytokinesis—the division of a cell into two daughter cells—is a key step in cell growth and proliferation. It typically occurs in synchrony with the cell cycle to ensure that a complete copy of the genetic information is passed on to the next generation of daughter cells. In animal cells, cytokinesis commonly relies on an actomyosin contractile ring that drives equatorial furrowing and separation into the two daughter cells. However, also contractile ring-independent forms of cell division are known that depend on substrate-mediated traction forces. Here, we report evidence of an as yet unknown type of contractile ring-independent cytokinesis that we termed wave-mediated cytofission. It is driven by self-organized cortical actin waves that travel across the ventral membrane of oversized, multinucleatedDictyostelium discoideumcells. Upon collision with the cell border, waves may initiate the formation of protrusions that elongate and eventually pinch off to form separate daughter cells. They are composed of a stable elongated wave segment that is enclosed by a cell membrane and moves in a highly persistent fashion. We rationalize our observations based on a noisy excitable reaction–diffusion model in combination with a dynamic phase field to account for the cell shape and demonstrate that daughter cells emerging from wave-mediated cytofission exhibit a well-controlled size.

scholarly journals Cytokinesis in Eukaryotic Cells: The Furrow Complexity at a Glance

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 271 ◽  
Author(s):  
Roberta Fraschini
Keyword(s):  
Cell Division ◽  
Asymmetric Cell Division ◽  
Animal Cell ◽  
Genetic Material ◽  
Model Organism ◽  
Complex Phase ◽  
Daughter Cells ◽  
Viable Cells ◽  
A Cell ◽  
Duplication Cycle

The duplication cycle is the fascinating process that, starting from a cell, results in the formation of two daughter cells and it is essential for life. Cytokinesis is the final step of the cell cycle, it is a very complex phase, and is a concert of forces, remodeling, trafficking, and cell signaling. All of the steps of cell division must be properly coordinated with each other to faithfully segregate the genetic material and this task is fundamental for generating viable cells. Given the importance of this process, molecular pathways and proteins that are involved in cytokinesis are conserved from yeast to humans. In this review, we describe symmetric and asymmetric cell division in animal cell and in a model organism, budding yeast. In addition, we illustrate the surveillance mechanisms that ensure a proper cell division and discuss the connections with normal cell proliferation and organs development and with the occurrence of human diseases.

Ultrastructure of mitosis in the chloromonadophycean alga Vacuolaria virescens

1978 ◽  
Vol 31 (1) ◽  
pp. 37-51
Author(s):  
P. Heywood
Keyword(s):  
Golgi Apparatus ◽  
Nuclear Envelope ◽  
Genetic Material ◽  
Membrane Vesicles ◽  
Contractile Vacuole ◽  
Basal Bodies ◽  
Anterior Surface ◽  
Daughter Cells ◽  
Interphase Cells ◽  
Unusual Type

During preprophase in the chloromonadophycean alga Vacuolaria virescens microtubules are present around the flagellar basal bodies and extend over the anterior surface of the nucleus. These microtubules assist in the separation of the flagella and later enter the nucleus through polar gaps. During prophase the nucleoli begin to disperse and the chromosomes become condensed. At metaphase the nucleus assumes an elliptical shape and an equatorial plate of chromosomes becomes aligned across the long axis of the nucleus; kinetochores are recognizable on some of the chromosomes. The nuclear envelope remains intact over most of the surface and in places it forms folds. During anaphase chromosomes are less distinct and vesicles are present in the elongating nucleus. Most of the new nuclear envelope around the progeny nuclei is formed by coalescence of these membrane vesicles during late anaphase and telophase, although some of the original nuclear envelope may also become incorporated. During telophase disintegration of the original nuclear envelope becomes pronounced and portions of this structure are recognizable in the cytoplasm after completion of mitosis. It is suggested that this unusual type of nuclear envelope behaviour may be important in ensuring the segregation of the Golgi apparatus and contractile vacuole to progeny cells. Interphase cells contain a single extensive Golgi apparatus which is located between the anterior surface of the nucleus and the contractile vacuole. The Golgi apparatus and contractile vacuole act as an osmoregulatory system and their presence is presumably essential to the existence of the organism. Formation of a new contractile vacuole and division of the Golgi apparatus occur early in mitosis and thereafter a Golgi apparatus and contractile vacuole become associated with each of the poles of the nucleus. They retain this location throughout mitosis and during cytokinesis, with the result that an osmoregulatory system is present in each of the daughter cells. In a similar manner, microbody-like organelles are associated with the nuclear envelope during mitosis but not at interphase. Growth of the nuclear envelope during mitosis may serve as the means of partitioning these organelles to the progeny cells. Thus mitosis in Vacuolaria virescens is responsible not only for the equal segregation of the genetic material but also for the correct distribution of some of the cytoplasmic components.

SYMPOSIUM ON CONGENITAL METABOLIC DISEASE

PEDIATRICS ◽  
1958 ◽  
Vol 21 (6) ◽  
pp. 1018-1021
Author(s):  
Charles U. Lowe ◽  
Barton Childs
Keyword(s):  
Gene Action ◽  
Genetic Material ◽  
Basic Mechanism ◽  
Reaction Rates ◽  
Human Beings ◽  
Secondary Effects ◽  
Genetic Origin ◽  
Daughter Cells ◽  
Metabolic Functions ◽  
Definition Of

MOST of the conditions to be considered in this symposium share one feature: their genetic origin. It could be profitable then to outline some of the principles of gene action and of the characteristics of genetic disease which will apply equally to all of the disorders to be reviewed. To begin, a definition of gene action is offered. This must be an empirical one since it is not known, with any precision, what a gene is. However, it is known that the genetic material provides the most basic mechanism for homeostasis, ensuring that offspring will exhibit the characteristics of the parent, whether the offspring be daughter cells or human beings. This is accomplished by means of control over the formation and design of the vital molecules of the organism; those molecules which in their turn control its intricate and interrealted metabolic functions. It is for the most part these metabolic functions which we attempt to measure in the elucidation of gene action in disease, and it will be seen in the ensuing discussions that only rarely is one able to make any direct assessment of the physicochemical properties of these molecules which bear a specific relationship to the gene. Much more commonly, a measurement is made of some form of activity of such substances, and a stepwise elucidation may be accomplished of the secondary effects which are consequent upon alterations in reaction rates or reaction failure. It is, in general, these secondary, tertiary, or consequential effects which are most easily measured, and which are the overt expressions of the disease. The principle illustrated here is, what a gene is said to do, depends upon which function we measure.

scholarly journals Cytokinesis in Eukaryotes

2002 ◽  
Vol 66 (2) ◽  
pp. 155-178 ◽  
Author(s):  
David A. Guertin ◽  
Susanne Trautmann ◽  
Dannel McCollum
Keyword(s):  
Genetic Model ◽  
Plant Cells ◽  
Complex Problem ◽  
Model Organisms ◽  
Animal Cells ◽  
Contractile Ring ◽  
Daughter Cells ◽  
Intense Research

SUMMARY Cytokinesis is the final event of the cell division cycle, and its completion results in irreversible partition of a mother cell into two daughter cells. Cytokinesis was one of the first cell cycle events observed by simple cell biological techniques; however, molecular characterization of cytokinesis has been slowed by its particular resistance to in vitro biochemical approaches. In recent years, the use of genetic model organisms has greatly advanced our molecular understanding of cytokinesis. While the outcome of cytokinesis is conserved in all dividing organisms, the mechanism of division varies across the major eukaryotic kingdoms. Yeasts and animals, for instance, use a contractile ring that ingresses to the cell middle in order to divide, while plant cells build new cell wall outward to the cortex. As would be expected, there is considerable conservation of molecules involved in cytokinesis between yeast and animal cells, while at first glance, plant cells seem quite different. However, in recent years, it has become clear that some aspects of division are conserved between plant, yeast, and animal cells. In this review we discuss the major recent advances in defining cytokinesis, focusing on deciding where to divide, building the division apparatus, and dividing. In addition, we discuss the complex problem of coordinating the division cycle with the nuclear cycle, which has recently become an area of intense research. In conclusion, we discuss how certain cells have utilized cytokinesis to direct development.

scholarly journals Mechanical Mechanisms of Chromosome Segregation

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 465
Author(s):  
Maya I. Anjur-Dietrich ◽  
Colm P. Kelleher ◽  
Daniel J. Needleman
Keyword(s):  
Cell Division ◽  
Chromosome Segregation ◽  
Genetic Material ◽  
Evolutionary Genetics ◽  
Force Generation ◽  
Coarse Grained ◽  
Subcellular Structure ◽  
Daughter Cells ◽  
The Past ◽  
The Future

Chromosome segregation—the partitioning of genetic material into two daughter cells—is one of the most crucial processes in cell division. In all Eukaryotes, chromosome segregation is driven by the spindle, a microtubule-based, self-organizing subcellular structure. Extensive research performed over the past 150 years has identified numerous commonalities and contrasts between spindles in different systems. In this review, we use simple coarse-grained models to organize and integrate previous studies of chromosome segregation. We discuss sites of force generation in spindles and fundamental mechanical principles that any understanding of chromosome segregation must be based upon. We argue that conserved sites of force generation may interact differently in different spindles, leading to distinct mechanical mechanisms of chromosome segregation. We suggest experiments to determine which mechanical mechanism is operative in a particular spindle under study. Finally, we propose that combining biophysical experiments, coarse-grained theories, and evolutionary genetics will be a productive approach to enhance our understanding of chromosome segregation in the future.

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