Cyclin-dependent kinase
[3][4] The catalytic activities of CDKs are regulated by interactions with CDK inhibitors (CKIs) and regulatory subunits known as cyclins.
This motif ensures CDKs accurately target and modify proteins, crucial for regulating cell cycle and other functions.
[7] Deregulation of the CDK activity is linked to various pathologies, including cancer, neurodegenerative diseases, and stroke.
[6] CDKs were initially identified through studies in model organisms such as yeasts and frogs, underscoring their pivotal role in cell cycle progression.
Over the years, the understanding of CDKs has expanded beyond cell division to include roles in gene transcription integration of cellular signals.
[7][8] The evolutionary journey of CDKs has led to a diverse family with specific members dedicated to cell cycle phases or transcriptional control.
This evolutionary expansion from simple regulators to multifunctional enzymes underscores the critical importance of CDKs in the complex regulatory networks of eukaryotic cells.
[7] In 2001, the scientists Leland H. Hartwell, Tim Hunt and Sir Paul M. Nurse were awarded the Nobel Prize in Physiology or Medicine for their discovery of key regulators of the cell cycle.
This phosphorylation typically occurs on a specific threonine residue, leading to a conformational change in the CDK that enhances its kinase activity.
[13] The activation forms a cyclin-CDK complex which phosphorylates specific regulatory proteins that are required to initiate steps in the cell-cycle.
Research on the structure of human CDK2 has shown that CDKs have a specially adapted ATP-binding site that can be regulated through the binding of cyclin.
This illustrates the complexity and fine-tuning in the regulation of the cell cycle through selective binding and activation of CDKs by their respective cyclins.
Ligand-based inhibition methods involve the use of small molecules or ligands that specifically bind to CDK2, which is a crucial regulator of the cell cycle.
This binding increases the affinity of the cyclin-CDK complex for its substrates, especially those with multiple phosphorylation sites, thus contributing the promotion of cell proliferation.
[22] p35 and p39 play a crucial role in a unique mechanism for regulating CDK5 activity in neuronal development and network formation.
Originally identified in Xenopus, these proteins primarily bind to and activate CDK1 and CDK2, despite lacking homology to cyclins.
[24] The dysregulation of CDKs and cyclins disrupts the cell cycle coordination, which makes them involved in the pathogenesis of several diseases, mainly cancers.
Thus, studies of cyclins and cyclin-dependent kinases (CDK) are essential for advancing the understanding of cancer characteristics.
[2] The dysregulation of the CDK4/6-RB pathway is a common feature in many cancers, often resulting from various mechanisms that inactivate the cyclin D-CDK4/6 complex.
[30] More research is required, however, because disruption of the CDK-mediated pathway has potentially serious consequences; while CDK inhibitors seem promising, it has to be determined how side-effects can be limited so that only target cells are affected.
[31] The comparison with glucocorticoids serves to illustrate the potential benefits of CDK inhibitors, assuming their side effects can be more narrowly targeted or minimized.
