Physiological Relevance of Cell Cycle Kinases

2011 ◽  
Vol 91 (3) ◽  
pp. 973-1007 ◽  
Author(s):  
Marcos Malumbres
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Human Disease ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Mitotic Checkpoint ◽  
Model Organisms ◽  
Cell Cycle Regulators ◽  
Therapeutic Benefits ◽  
Physiological Relevance

The basic biology of the cell division cycle and its control by protein kinases was originally studied through genetic and biochemical studies in yeast and other model organisms. The major regulatory mechanisms identified in this pioneer work are conserved in mammals. However, recent studies in different cell types or genetic models are now providing a new perspective on the function of these major cell cycle regulators in different tissues. Here, we review the physiological relevance of mammalian cell cycle kinases such as cyclin-dependent kinases (Cdks), Aurora and Polo-like kinases, and mitotic checkpoint regulators (Bub1, BubR1, and Mps1) as well as other less-studied enzymes such as Cdc7, Nek proteins, or Mastl and their implications in development, tissue homeostasis, and human disease. Among these functions, the control of self-renewal or asymmetric cell division in stem/progenitor cells and the ability to regenerate injured tissues is a central issue in current research. In addition, many of these proteins play previously unexpected roles in metabolism, cardiovascular function, or neuron biology. The modulation of their enzymatic activity may therefore have multiple therapeutic benefits in human disease.

scholarly journals Coordinating cell polarity and cell cycle progression: what can we learn from flies and worms?

Open Biology ◽  
2013 ◽  
Vol 3 (8) ◽  
pp. 130083 ◽  
Author(s):  
Anna Noatynska ◽  
Nicolas Tavernier ◽  
Monica Gotta ◽  
Lionel Pintard
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Fate ◽  
Cell Polarity ◽  
Cell Cycle Progression ◽  
Molecular Mechanisms ◽  
Asymmetric Cell Division ◽  
Control Cell ◽  
Model Organisms ◽  
Cycle Progression

Spatio-temporal coordination of events during cell division is crucial for animal development. In recent years, emerging data have strengthened the notion that tight coupling of cell cycle progression and cell polarity in dividing cells is crucial for asymmetric cell division and ultimately for metazoan development. Although it is acknowledged that such coupling exists, the molecular mechanisms linking the cell cycle and cell polarity machineries are still under investigation. Key cell cycle regulators control cell polarity, and thus influence cell fate determination and/or differentiation, whereas some factors involved in cell polarity regulate cell cycle timing and proliferation potential. The scope of this review is to discuss the data linking cell polarity and cell cycle progression, and the importance of such coupling for asymmetric cell division. Because studies in model organisms such as Caenorhabditis elegans and Drosophila melanogaster have started to reveal the molecular mechanisms of this coordination, we will concentrate on these two systems. We review examples of molecular mechanisms suggesting a coupling between cell polarity and cell cycle progression.

scholarly journals Generation of asymmetry during development. Segregation of type-specific proteins in Caulobacter.

1979 ◽  
Vol 81 (1) ◽  
pp. 123-136 ◽  
Author(s):  
N Agabian ◽  
M Evinger ◽  
G Parker
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Messenger Rna ◽  
Cell Types ◽  
Specific Protein ◽  
Soluble Proteins ◽  
Specific Cell ◽  
Daughter Cells ◽  
Specific Proteins ◽  
Entire Cell

An essential event in developmental processes is the introduction of asymmetry into an otherwise undifferentiated cell population. Cell division in Caulobacter is asymmetric; the progeny cells are structurally different and follow different sequences of development, thus providing a useful model system for the study of differentiation. Because the progeny cells are different from one another, there must be a segregation of morphogenetic and informational components at some time in the cell cycle. We have examined the pattern of specific protein segregation between Caulobacter stalked and swarmer daughter cells, with the rationale that such a progeny analysis would identify both structurally and developmentally important proteins. To complement the study, we have also examined the pattern of protein synthesis during synchronous growth and in various cellular fractions. We show here, for the first time, that the association of proteins with a specific cell type may result not only from their periodicity of synthesis, but also from their pattern of distribution at the time of cell division. Several membrane-associated and soluble proteins are segregated asymmetrically between progeny stalked and swarmer cells. The data further show that a subclass of soluble proteins becomes associated with the membrane of the progeny stalked cells. Therefore, although the principal differentiated cell types possess different synthetic capabilities and characteristic proteins, the asymmetry between progeny stalked and swarmer cells is generated primarily by the preferential association of specific soluble proteins with the membrane of only one daughter cell. The majority of the proteins which exhibit this segregation behavior are synthesized during the entire cell cycle and exhibit relatively long, functional messenger RNA half-lives.

scholarly journals Cell growth dilutes the cell cycle inhibitor Rb to trigger cell division

2018 ◽  
Author(s):  
Evgeny Zatulovskiy ◽  
Daniel F. Berenson ◽  
Benjamin R. Topacio ◽  
Jan M. Skotheim
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Growth ◽  
Cell Size ◽  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Inverse Correlation ◽  
Cell Types ◽  
Similar Amount ◽  
Cell Cycle Inhibitor

Cell size is fundamental to function in different cell types across the human body because it sets the scale of organelle structures, biosynthesis, and surface transport1,2. Tiny erythrocytes squeeze through capillaries to transport oxygen, while the million-fold larger oocyte divides without growth to form the ~100 cell pre-implantation embryo. Despite the vast size range across cell types, cells of a given type are typically uniform in size likely because cells are able to accurately couple cell growth to division3–6. While some genes whose disruption in mammalian cells affects cell size have been identified, the molecular mechanisms through which cell growth drives cell division have remained elusive7–12. Here, we show that cell growth acts to dilute the cell cycle inhibitor Rb to drive cell cycle progression from G1 to S phase in human cells. In contrast, other G1/S regulators remained at nearly constant concentration. Rb is a stable protein that is synthesized during S and G2 phases in an amount that is independent of cell size. Equal partitioning to daughter cells of chromatin bound Rb then ensures that all cells at birth inherit a similar amount of Rb protein. RB overexpression increased cell size in tissue culture and a mouse cancer model, while RB deletion decreased cell size and removed the inverse correlation between cell size at birth and the duration of G1 phase. Thus, Rb-dilution by cell growth in G1 provides a long-sought cell autonomous molecular mechanism for cell size homeostasis.

scholarly journals Checkpoint signaling abrogation after cell cycle reentry reveals that differentiated neurons are mitotic cells

2018 ◽  
Author(s):  
Chaska C Walton ◽  
Wei Zhang ◽  
Iris Patiño-Parrado ◽  
Estíbaliz Barrio-Alonso ◽  
Juan-José Garrido ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Cell Division ◽  
Mitotic Activity ◽  
Cell Cycle Progression ◽  
Cyclin E ◽  
Mitotic Checkpoint ◽  
Checkpoint Signaling ◽  
Cell Cycle Reentry ◽  
Mitotic Cells

SUMMARYMitotic activity associated to neuron cell-death instead of cell-division is reported in neurodegenerative diseases. However, why mitotic activity can take place in supposedly postmitotic neurons and how it is associated to cell-death remains largely unexplained. To address these questions, we have studied the response of primary neurons to oncogenic deregulation using a fusion protein based on truncated Cyclin E and Cdk2. Oncogenic Cyclin E/Cdk2 elicits mitotic checkpoint signaling, resulting in cell-cycle arrest and cell-death. However, as in mitotic cells, checkpoint suppression enables oncogenic cell-cycle progression and neuronal division. Further, neurons actively adapt to the cell-cycle by losing and reforming the axon initial segment, which integrates synaptic inputs to sustain action potentials. We conclude that neurons are mitotic cells in a reversible quiescent-like state, which is falsely portrayed as irreversible by mitotic checkpoints. In extension, neuronal death in lieu of cell-division reflects oncosuppressive checkpoint signaling.

scholarly journals Endodermal differentiation is reconstructed by coordination of two parallel signaling systems derived from the stele in roots

2017 ◽  
Author(s):  
Pengxue Li ◽  
Qiaozhi Yu ◽  
Chunmiao Xu ◽  
Xu Gu ◽  
Shilian Qi ◽  
...  
Keyword(s):  
Cell Division ◽  
Cell Fate ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Plant Roots ◽  
Synthetic Approach ◽  
Fate Map ◽  
Signaling Systems ◽  
Apoplastic Barrier ◽  
Casparian Strips

AbstractThe plant roots represent the exquisitely controlled cell fate map in which different cell types undergo a complete status transition from stem cell division and initial fate specification, to the terminal differentiation. The endodermis is initially specified in meristem but further differentiates to form Casparian strips (CSs), the apoplastic barrier in the mature zone for the selective transport between stele and outer tissues, and thus is regarded as plant inner skin. In the Arabidopsis thaliana root the transcription factors SHORTROOT (SHR) regulate asymmetric cell division in cortical initials to separate endodermal and cortex cell layer. In this paper, we utilized synthetic approach to examine the reconstruction of fully functional Casparian strips in plant roots. Our results revealed that SHR serves as a master regulator of a hierarchical signaling cascade that, combined with stele-derived small peptides, is sufficient to rebuild the functional CS in non-endodermal cells. This is a demonstration of the deployment of two parallel signaling systems, in which both apoplastic and symplastic communication were employed, for coordinately specifying the endodermal cell fate.

scholarly journals Analysis of Cell Cycle Progression in the Budding Yeast S. cerevisiae

2021 ◽  
pp. 265-276
Author(s):  
Deniz Pirincci Ercan ◽  
Frank Uhlmann
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Cell Cycle Progression ◽  
Budding Yeast ◽  
Expression Profiles ◽  
Model Organisms ◽  
Cyclin Dependent Kinase ◽  
Cycle Progression ◽  
Daughter Cells ◽  
Substrate Phosphorylation

AbstractThe cell cycle is an ordered series of events by which cells grow and divide to give rise to two daughter cells. In eukaryotes, cyclin–cyclin-dependent kinase (cyclin–Cdk) complexes act as master regulators of the cell division cycle by phosphorylating numerous substrates. Their activity and expression profiles are regulated in time. The budding yeast S. cerevisiae was one of the pioneering model organisms to study the cell cycle. Its genetic amenability continues to make it a favorite model to decipher the principles of how changes in cyclin-Cdk activity translate into the intricate sequence of substrate phosphorylation events that govern the cell cycle. In this chapter, we introduce robust and straightforward methods to analyze cell cycle progression in S. cerevisiae. These techniques can be utilized to describe cell cycle events and to address the effects of perturbations on accurate and timely cell cycle progression.

scholarly journals Roles of Actin in the Morphogenesis of the Early Caenorhabditis elegans Embryo

2020 ◽  
Vol 21 (10) ◽  
pp. 3652
Author(s):  
Dureen Samandar Eweis ◽  
Julie Plastino
Keyword(s):  
Cell Division ◽  
Caenorhabditis Elegans ◽  
Asymmetric Cell Division ◽  
Cell Types ◽  
Actin Dynamics ◽  
Actin Binding ◽  
Asymmetric Cell Divisions ◽  
C Elegans ◽  
Asymmetric Divisions ◽  
Different Cell Types

The cell shape changes that ensure asymmetric cell divisions are crucial for correct development, as asymmetric divisions allow for the formation of different cell types and therefore different tissues. The first division of the Caenorhabditis elegans embryo has emerged as a powerful model for understanding asymmetric cell division. The dynamics of microtubules, polarity proteins, and the actin cytoskeleton are all key for this process. In this review, we highlight studies from the last five years revealing new insights about the role of actin dynamics in the first asymmetric cell division of the early C. elegans embryo. Recent results concerning the roles of actin and actin binding proteins in symmetry breaking, cortical flows, cortical integrity, and cleavage furrow formation are described.

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