ChemInform Abstract: Cyclin-Dependent Kinases and Cell Cycle Control (Nobel Lecture).

ChemInform ◽  
2010 ◽  
Vol 33 (36) ◽  
pp. no-no
Author(s):  
Paul Nurse
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Nobel Lecture ◽  
Cyclin Dependent Kinases

NOBEL LECTURE: Cyclin Dependent Kinases and Cell Cycle Control

2002 ◽  
Vol 22 (5-6) ◽  
pp. 487-499 ◽  
Author(s):  
Paul M. Nurse
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Eukaryotic Cell ◽  
Nobel Lecture ◽  
Cyclin Dependent Kinases

The discovery of major regulators of the eukaryotic cell cycle is described.

scholarly journals Cell cycle analysis of the activity, subcellular localization, and subunit composition of human CAK (CDK-activating kinase).

1994 ◽  
Vol 127 (2) ◽  
pp. 467-478 ◽  
Author(s):  
J P Tassan ◽  
S J Schultz ◽  
J Bartek ◽  
E A Nigg
Keyword(s):  
Cell Cycle ◽  
Somatic Cell ◽  
Cell Cycle Control ◽  
Gel Filtration ◽  
Multiprotein Complex ◽  
Cyclin Dependent Kinases ◽  
Critical Residue ◽  
Cdk Activating Kinase

The activity of cyclin-dependent kinases (cdks) depends on the phosphorylation of a residue corresponding to threonine 161 in human p34cdc2. One enzyme responsible for phosphorylating this critical residue has recently been purified from Xenopus and starfish. It was termed CAK (for cdk-activating kinase), and it was shown to contain p40MO15 as its catalytic subunit. In view of the cardinal role of cdks in cell cycle control, it is important to learn if and how CAK activity is regulated during the somatic cell cycle. Here, we report a molecular characterization of a human p40MO15 homologue and its associated CAK activity. We have cloned and sequenced a cDNA coding for human p40MO15, and raised specific polyclonal and monoclonal antibodies against the corresponding protein expressed in Escherichia coli. These tools were then used to demonstrate that p40MO15 protein expression and CAK activity are constant throughout the somatic cell cycle. Gel filtration suggests that active CAK is a multiprotein complex, and immunoprecipitation experiments identify two polypeptides of 34 and 32 kD as likely complex partners of p40MO15. The association of the three proteins is near stoichiometric and invariant throughout the cell cycle. Immunocytochemistry and biochemical enucleation experiments both demonstrate that p40MO15 is nuclear at all stages of the cell cycle (except for mitosis, when the protein redistributes throughout the cell), although the p34cdc2/cyclin B complex, one of the major purported substrates of CAK, occurs in the cytoplasm until shortly before mitosis. The absence of obvious changes in CAK activity in exponentially growing cells constitutes a surprise. It suggests that the phosphorylation state of threonine 161 in p34cdc2 (and the corresponding residue in other cdks) may be regulated primarily by the availability of the cdk/cyclin substrates, and by phosphatase(s).

Distinct roles for cyclin-dependent kinases in cell cycle control

Science ◽  
1993 ◽  
Vol 262 (5142) ◽  
pp. 2050-2054 ◽  
Author(s):  
S van den Heuvel ◽  
E Harlow
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Control ◽  
Cyclin Dependent Kinases

scholarly journals Fission yeast cell cycle mutants and the logic of eukaryotic cell cycle control

2020 ◽  
Vol 31 (26) ◽  
pp. 2871-2873
Author(s):  
Paul Nurse
Keyword(s):  
Cell Cycle ◽  
Cell Division ◽  
Fission Yeast ◽  
Cell Cycle Control ◽  
Eukaryotic Cell ◽  
S Phase ◽  
Cyclin Dependent Kinases ◽  
Starting Point ◽  
Rate Limiting ◽  
Working Out

Cell cycle mutants in the budding and fission yeasts have played critical roles in working out how the eukaryotic cell cycle operates and is controlled. The starting point was Lee Hartwell’s 1970s landmark papers describing the first cell division cycle (CDC) mutants in budding yeast. These mutants were blocked at different cell cycle stages and so were unable to complete the cell cycle, thus defining genes necessary for successful cell division. Inspired by Hartwell’s work, I isolated CDC mutants in the very distantly related fission yeast. This started a program of searches for mutants in fission yeast that revealed a range of phenotypes informative about eukaryotic cell cycle control. These included mutants defining genes that were rate-limiting for the onset of mitosis and of the S-phase, that were responsible for there being only one S-phase in each cell cycle, and that ensured that mitosis only took place when S-phase was properly completed. This is a brief account of the discovery of these mutants and how they led to the identification of cyclin-dependent kinases as core to these cell cycle controls.

scholarly journals Core Control Principles of the Eukaryotic Cell Cycle

2021 ◽  
Author(s):  
Souradeep Basu ◽  
Paul Nurse ◽  
Andrew Jones
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Eukaryotic Cell ◽  
Protein Phosphatase 1 ◽  
Cycle Progression ◽  
Substrate Specificities ◽  
Cyclin Dependent Kinases ◽  
Do So

Abstract Cyclin dependent kinases (CDKs) lie at the heart of eukaryotic cell cycle control, with different Cyclin-CDK complexes initiating DNA replication (S-CDKs) and mitosis (M-CDKs). However, the principles on which Cyclin-CDKs organise the temporal order of cell cycle events are contentious. The currently most widely accepted model, is that the S-CDKs and M-CDKs are functionally specialised, with significant different substrate specificities to execute different cell cycle events. A second model is that S-CDKs and M-CDKs are redundant with each other, with both acting as sources of overall cellular CDK activity. Here we reconcile these two views of core cell cycle control. Using a multiplexed phosphoproteomics assay of in vivo S-CDK and M-CDK activities in fission yeast, we show that S-CDK and M-CDK substrate specificities are very similar, showing that S-CDKs are not completely specialised for S-phase alone. Normally S-CDK cannot undergo mitosis, but is able to do so when Protein Phosphatase 1 (PP1) is removed from the centrosome, allowing several mitotic substrates to be better phosphorylated by S-CDK in vivo. Thus, an increase in S-CDK activity in vivo is sufficient to allow S-CDK to carry out M-CDK function. Therefore, we unite the two opposing views of cell cycle control, showing that the core cell cycle engine which temporally orders cell cycle progression is largely based upon a quantitative increase of CDK activity through the cell cycle, combined with minor qualitative differences in catalytic specialisation of S-CDKs and M-CDKs.

scholarly journals Cyclin-Dependent Kinases and CTD Phosphatases in Cell Cycle Transcriptional Control: Conservation across Eukaryotic Kingdoms and Uniqueness to Plants

Cells ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 279
Author(s):  
Zhi-Liang Zheng
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase Ii ◽  
Large Scale ◽  
Transcriptional Control ◽  
Cell Cycle Control ◽  
Yeast Saccharomyces Cerevisiae ◽  
Pol Ii ◽  
Precise Control ◽  
Cyclin Dependent Kinases ◽  
Entire Cell

Cell cycle control is vital for cell proliferation in all eukaryotic organisms. The entire cell cycle can be conceptually separated into four distinct phases, Gap 1 (G1), DNA synthesis (S), G2, and mitosis (M), which progress sequentially. The precise control of transcription, in particular, at the G1 to S and G2 to M transitions, is crucial for the synthesis of many phase-specific proteins, to ensure orderly progression throughout the cell cycle. This mini-review highlights highly conserved transcriptional regulators that are shared in budding yeast (Saccharomyces cerevisiae), Arabidopsis thaliana model plant, and humans, which have been separated for more than a billion years of evolution. These include structurally and/or functionally conserved regulators cyclin-dependent kinases (CDKs), RNA polymerase II C-terminal domain (CTD) phosphatases, and the classical versus shortcut models of Pol II transcriptional control. A few of CDKs and CTD phosphatases counteract to control the Pol II CTD Ser phosphorylation codes and are considered critical regulators of Pol II transcriptional process from initiation to elongation and termination. The functions of plant-unique CDKs and CTD phosphatases in relation to cell division are also briefly summarized. Future studies towards testing a cooperative transcriptional mechanism, which is proposed here and involves sequence-specific transcription factors and the shortcut model of Pol II CTD code modulation, across the three eukaryotic kingdoms will reveal how individual organisms achieve the most productive, large-scale transcription of phase-specific genes required for orderly progression throughout the entire cell cycle.

scholarly journals CDKs family -a glimpse into the past and present: from cell cycle control to current biological functions

2020 ◽  
Vol 5 (1) ◽  
pp. 1-9
Author(s):  
Muzna Shah ◽  
Muhammad Fazal Hussain Qureshi ◽  
Danish Mohammad ◽  
Mahira Lakhani ◽  
Tabinda Urooj ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Mammalian Cells ◽  
Cell Cycle Progression ◽  
Cell Cycle Control ◽  
Cell Renewal ◽  
Catalytic Subunits ◽  
Cyclin Dependent Kinases ◽  
Stem Cell Renewal ◽  
Cyclin Protein ◽  
Cycle Regulation

Cyclin-dependent kinases (CDKs) are the catalytic subunits or protein kinases characterized by separate subunit “cyclin” that are essential for their enzymatic activity. CDKs play important roles in the control of cell cycle progression, cell division, neuronal function, epigenetic regulation, metabolism, stem cell renewal and transcription. However, they can accomplish some of these tasks independently, without binding with cyclin protein or kinase activity. Thus, so far, twenty different CDKs and cyclins have been reported in mammalian cells. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). In this review, we summarizes that how CDKs are traditionally involve their latest revelations, their functional diversity beyond cell cycle regulation and their impact on development of disease in mammals.  

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