Cdc2–cyclin E complexes regulate the G1/S phase transition

@article{Aleem2005Cdc2cyclinEC,  title={Cdc2–cyclin E complexes regulate the G1/S phase transition},  author={Eiman Aleem and Hiroaki Kiyokawa and Philipp Kaldis},  journal={Nature Cell Biology},  year={2005},  volume={7},  pages={831-836},  url={https://api.semanticscholar.org/CorpusID:10842071}}
In vivo results provide strong evidence that Cdc2 may compensate the loss of Cdk2 function, indicating a parallel pathway regulated by p27.

411 Citations

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Rb/Cdk2/Cdk4 triple mutant mice elicit an alternative mechanism for regulation of the G1/S transition

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Specialized roles of the two mitotic cyclins in somatic cells: cyclin A as an activator of M phase-promoting factor.

It is shown that down-regulation of cyclin A induces a G2 phase arrest through a checkpoint-independent inactivation ofcyclin B-CDC2 by inhibitory phosphorylation, and a critical role of Cyclin A as a trigger for MPF activation is underscore.

p27 as a Transcriptional Regulator: New Roles in Development and Cancer

Noncanonical, CDK-independent functions of p27 in migration, invasion, development, and gene expression are focused on, with emphasis on how transcriptional regulation by p27 illuminates its actions in cancer.

CDK redundancy guarantees cell cycle progression in RB-negative tumor cells independently of their p16 status

The results suggest that, despite their lack of cyclin D-containing complexes, Rb-negative tumor cells, like normal untransformed cells, take advantage of the high degree of redundancy of cdks for their cell cycle progression.

Cdk2 and Cdk4 Activities Are Dispensable for Tumorigenesis Caused by the Loss of p53

The results suggest that tumorigenicity mediated by p53 loss does not require either Cdk2 or Cdk4, which necessitates considering the use of broad-spectrum cell cycle inhibitors as a means of effective anti-Cdk cancer therapy.

Cdk2 and Cdk4 cooperatively control the expression of Cdc2

It is considered that the balance between proliferation and differentiation is disturbed, which affects especially heart development and leads to embryonic lethality in Cdk2-/-Cdk4-/- mutants.

Unmasking the Redundancy Between Cdk1 and Cdk2 at G2 Phase in Human Cancer Cell Lines

The results suggest that the redistributed complexes contribute to the cyclin B-Cdk1 activation when either Cdk1 or Cdk2 alone is ablated and this redundancy masks C DK2’s role when Cdk 2 is singly ablated.
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24 References

Targeted Disruption of CDK4 Delays Cell Cycle Entry with Enhanced p27Kip1 Activity

Results suggest that at least part of CDK4’s participation in the rate-limiting mechanism for the G0-S transition consists of controlling p27 activity, which is opposite to those of p27-deficient mice.

p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.

Cyclin D2-Cdk4 complexes bind competitively to and down-regulate the activity of p27 and may thereby act in a pathway that reverses Cdk2 inhibition and enables G1 progression.

Cooperation between Cdk4 and p27kip1 in tumor development: a preclinical model to evaluate cell cycle inhibitors with therapeutic activity.

It is shown here that exposure to flavopiridol, a wide-spectrum Cdk inhibitor, significantly delays tumor progression and leads to tumor-free survival in a significant percentage of treated mice, suggesting that genetically engineered tumor models involving key cell cycle regulators are a valuable tool to evaluate drugs with potential therapeutic benefit in human cancer.

Cdk2 as a Master of S phase Entry: Fact or Fake?

The purpose of this mini-review is to compare both Cdk2 and cyclin E knockout mice models and to discuss potential mechanisms driving the cell cycle in the absence of Cdk1 or cyclin F, with particular emphasis on possible non-catalytic roles ofcyclin E.

CDK inhibitors: positive and negative regulators of G1-phase progression.

This work challenges previous assumptions about how the G1/S transition of the mammalian cell cycle is governed, helps explain some enigmatic features of cell cycle control that also involve the functions of the retinoblastoma protein (Rb) and the INK4 proteins, and changes the thinking about how either p16 loss or overexpression of cyclin D-dependent kinases contribute to cancer.

D-type cyclin-dependent kinase activity in mammalian cells

Despite continued enforced overproduction of cyclins and cdk4, the assembly of cyclin D-cdk4 complexes and the appearance of their kinase activities remained dependent upon serum stimulation, indicating that upstream regulators must govern formation of the active enzymes.

A Centrosomal Localization Signal in Cyclin E Required for Cdk2-Independent S Phase Entry

Results suggest that cyclin E has a modular centrosomal-targeting domain essential for promoting S phase entry in a Cdk2-independent manner.

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