A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4

@article{Serrano1993ANR,
  title={A new regulatory motif in cell-cycle control causing specific inhibition of cyclin D/CDK4},
  author={M Serrano and Gregory J. Hannon and David H. Beach},
  journal={Nature},
  year={1993},
  volume={366},
  pages={704-707}
}
THE division cycle of eukaryotic cells is regulated by a family of protein kinases known as the cyclin-dependent kinases (CDKs)1,2. The sequential activation of individual members of this family and their consequent phosphorylation of critical substrates promotes orderly progression through the cell cycle3,4. The complexes formed by CDK4 and the D-type cyclins have been strongly implicated in the control of cell proliferation during the G1 phase3–6. CDK4 exists, in part, as a multi-protein… 
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Chapter 25. Cell Cycle Control and Cancer

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The structure reveals that p18(INK4c) inhibits the CDK-cyclin complex by distorting the ATP binding site and misaligning catalytic residues, and this structure provides insights into the specificity of the D-type cyclins for Cdk4/6.

Transcriptional repression of the D-type cyclin-dependent kinase inhibitor p16 by the retinoblastoma susceptibility gene product pRb.

It is reported that the p16 mRNA accumulates to a high level in cells lacking pRb function and transcription of p16 is repressed by pR b, providing evidence supporting a feedback regulatory loop involving pRB, p16, and cyclin-dependent kinases.

The Cyclin/Cyclin-Dependent Kinase (cdk) Complex: Regulation of Cell Cycle Progression and Nuclear Disassembly

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Formation of p27-CDK complexes during the human mitotic cell cycle.

  • T. SoosH. Kiyokawa A. Koff
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It is reported that, in MANCA cells, the amount of p27 is constant during the cell cycle and this data are consistent with a model wherein cyclin D/CDK complexes sequester the CDK2-dependent kinase inhibitory activity of p 27.

Conditional binding to and cell cycle-regulated inhibition of cyclin-dependent kinase complexes by p27Kip1.

Evidence is provided for cross-talk between the acquisition of quiescence, cdk activity, and G1 traverse and the results suggest an interplay between these two cell cycle transitions.

Regulation of CDK7–Carboxyl-Terminal Domain Kinase Activity by the Tumor Suppressor p16INK4A Contributes to Cell Cycle Regulation

The results suggest that p16INK4A may regulate cell cycle progression by inhibiting not only CDK4-pRb kinase activity but also by modulating CDK7-CTD kinases activity.

Advances in Brief Transcriptional Repression of the D-Type Cyclin-dependent Kinase Inhibitor p 16 by the Retinoblastoma Susceptibility Gene Product pRbt

It is reported that the p16 mRNA accumulates to a high level in cells lacking pRb function and transcription ofpl6 is repressed by pR b, providing evidence supporting a feedback regulatory loop involving pRB, p16, and cydin-dependent kinases.
...

References

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