Preparing a cell for nuclear envelope breakdown: Spatio‐temporal control of phosphorylation during mitotic entry

Álvarez-Fernández, Mónica; Malumbres, Marcos

doi:10.1002/bies.201400040

Cited by 24 publications

(22 citation statements)

References 94 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Changes in localisation that are likely dependent on specific thresholds in Cdk1 activity could also provide a potential delay mechanism. This has been observed for a variety of G2/M regulators such as Cdc25s, Wee1, Plk1, cyclin B, and Greatwall (reviewed by Refs ).…”

Section: Organising Mitosis: Open Questions In the Mitotic Entry Fieldmentioning

confidence: 70%

“…We will conclude this review with a brief outlook on how and why cancer cells might have changed the G2/M switch system, and how this could be further exploited by therapeutic intervention. For other aspects of mitotic entry dynamics, such as spatial regulation and functions of other mitotic kinases, the reader is referred to excellent recent reviews .…”

Section: The Mitotic Trigger Is An Irreversible Cellular Switchmentioning

confidence: 99%

“…The specific subcellular localisation and sequestration of the various kinases, phosphatases and other regulatory proteins that contribute to the Cdk1 activation feedback loops constitute another critical aspect of this switch system. This is likely to promote robust timing of mitotic events (reviewed by Refs ). A comprehensive numerical model of mitotic entry should incorporate both spatial and temporal regulation to fully capture these important features of mitotic control.…”

Section: Organising Mitosis: Open Questions In the Mitotic Entry Fieldmentioning

confidence: 99%

See 2 more Smart Citations

Triggering mitosis

Crncec

Hochegger

2019

FEBS Letters

View full text Add to dashboard Cite

Entry into mitosis is triggered by the activation of cyclin‐dependent kinase 1 (Cdk1). This simple reaction rapidly and irreversibly sets the cell up for division. Even though the core step in triggering mitosis is so simple, the regulation of this cellular switch is highly complex, involving a large number of interconnected signalling cascades. We do have a detailed knowledge of most of the components of this network, but only a poor understanding of how they work together to create a precise and robust system that ensures that mitosis is triggered at the right time and in an orderly fashion. In this review, we will give an overview of the literature that describes the Cdk1 activation network and then address questions relating to the systems biology of this switch. How is the timing of the trigger controlled? How is mitosis insulated from interphase? What determines the sequence of events, following the initial trigger of Cdk1 activation? Which elements ensure robustness in the timing and execution of the switch? How has this system been adapted to the high levels of replication stress in cancer cells?

show abstract

Section: Organising Mitosis: Open Questions In the Mitotic Entry Fieldmentioning

confidence: 70%

Section: The Mitotic Trigger Is An Irreversible Cellular Switchmentioning

confidence: 99%

Section: Organising Mitosis: Open Questions In the Mitotic Entry Fieldmentioning

confidence: 99%

See 1 more Smart Citation

Triggering mitosis

Crncec

Hochegger

2019

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Furthermore, autophagosomal engulfment of mitotic chromosomes was reported in mitotic cells undergoing programmed cell death (30), suggesting that autophagy inhibition may, indeed, protect the condensed genome from accidental autophagic engulfment. Moreover, during cell division, mitochondria and the Golgi apparatus become fragmented to facilitate their distribution between the two daughter cells (31, 32). While elongated mitochondria are spared from autophagic degradation (33, 34), the smaller size of fragmented mitochondria facilitates their uptake by autophagosomes (35, 36).…”

Section: Autophagy Status During Cell-cycle Progressionmentioning

confidence: 99%

Autophagy and the Cell Cycle: A Complex Landscape

2017

View full text Add to dashboard Cite

Autophagy is a self-degradation pathway, in which cytoplasmic material is sequestered in double-membrane vesicles and delivered to the lysosome for degradation. Under basal conditions, autophagy plays a homeostatic function. However, in response to various stresses, the pathway can be further induced to mediate cytoprotection. Defective autophagy has been linked to a number of human pathologies, including neoplastic transformation, even though autophagy can also sustain the growth of tumor cells in certain contexts. In recent years, a considerable correlation has emerged between autophagy induction and stress-related cell-cycle responses, as well as unexpected roles for autophagy factors and selective autophagic degradation in the process of cell division. These advances have obvious implications for our understanding of the intricate relationship between autophagy and cancer. In this review, we will discuss our current knowledge of the reciprocal regulation connecting the autophagy pathway and cell-cycle progression. Furthermore, key findings involving nonautophagic functions for autophagy-related factors in cell-cycle regulation will be addressed.

show abstract

“…At the entry of mitosis, more than several thousands of residues have been known to be phosphorylated (1, 2). A number of kinases which function in mitosis, such as CDK1, Aurora kinase, Plk1, Bub1, and Haspin, etc., have been identified (reviewed in (17–21)). Dephosphorylation also plays essential roles both at the entry and the exit of mitosis (22, 23) (24, 25).…”

Section: Introductionmentioning

confidence: 99%

Quantitative proteomics indicate a strong correlation of mitotic phospho-/dephosphorylation with non-structured regions of substrates

Yamazaki

Kosako

Yoshimura

2019

Preprint

View full text Add to dashboard Cite

16Protein phosphorylation plays inevitable roles in the regulation and the progression of mitosis. More than ten 17 thousands of phosphorylated residues and their responsible kinases have so far been identified by a number of 18 proteomic analyses. While some of those phosphosites have been demonstrated to affect either protein-protein 19 interaction or catalytic activity of the substrate protein, the effect of most mitotic phosphosites remain 20 unclarified. In this study, we tried to extract structural properties of mitotic phosphosites and neighboring 21 residues, and find a role of heavy phosphorylation at non-structured domain. A quantitative mass spectrometry 22 of mitosis-arrested and non-arrested HeLa cells identified more than 4,100 and 1,900 residues which are 23 significantly phosphorylated, and dephosphorylated at mitotic entry, respectively. Calculating the disorder score 24 of the neighboring amino acid sequence of individual phosphosites revealed that more than 70% of the 25 phosphosites which are dephosphorylated existed in disordered regions, whereas 50% of phosphorylated sites 26 existed in non-structured domain. There was a clear inversed co-relation between probability in non-structured 27 domain and increment of phosphorylation in mitosis. These results indicate that at the entry of mitosis, a 28 significant amount of phosphate group is removed from non-structured domains and attached to more structured 29 domains. GO term analysis revealed that mitosis-related proteins are heavily phosphorylated, whereas RNA-30 related proteins are both dephosphorylated and phosphorylated, implying that heavy 31 phosphorylation/dephosphorylation in non-structured domain of RNA-binding proteins may play a role in 32 dynamic rearrangement of RNA-containing organelle, as well as other intracellular environments. 33 34 65been identified (reviewed in (17-21)). Dephosphorylation also plays essential roles both at the entry and the 66 exit of mitosis (22, 23) (24, 25). More than 1,000 kinds of phosphosites are dephosphorylated during anaphase 67 (26), and more than five hundreds are dephosphorylated at the entry of mitosis (2). For example, CDK1 is 68 activated by dephosphorylation by Cdc25B/C (27, 28), and Cdc25C is partially activated by protein phosphatase 69 1 (27). These results indicate that a vast number of phosphate groups are transferred to and from the substrate 70 proteins during mitotic entry. 71One of the unclarified problems on mitotic phosphorylation could be why and how a vast number of 72 phosphate groups are transferred from a set of proteins to a different set of proteins, and whether these different 73 sets of mitotic phosphosites are structurally different or not. Especially, the distribution of phosphosites in 74 structured or non-structured regions of the substrate proteins is an important cue to understand the structural 75 effect of phosphorylation/dephosphorylation. In this study, we performed phosphoproteomic analysis of cellular 76 proteins to quantify and compare individual phosphosi...

show abstract

Preparing a cell for nuclear envelope breakdown: Spatio‐temporal control of phosphorylation during mitotic entry

Cited by 24 publications

References 94 publications

Triggering mitosis

Triggering mitosis

Autophagy and the Cell Cycle: A Complex Landscape

Quantitative proteomics indicate a strong correlation of mitotic phospho-/dephosphorylation with non-structured regions of substrates

Contact Info

Product

Resources

About