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[[File:Role_of_CDK4,_cyklin_D,_Rb_and_E2F_in_cell_cycle_regulation.jpg|thumb]] [[Image:Signal_transduction_pathways.svg|thumb]] '''Cyclin-dependent kinase 4''' ('''CDK4''') is an enzyme that in humans is encoded by the ''CDK4'' gene. CDK4 is a member of the [[cyclin-dependent kinase]] family. This family of [[protein kinases]] is highly conserved across the [[eukaryotes]] and has been shown to be involved in [[cell cycle]] regulation. CDK4, in particular, plays a critical role in the transition from the [[G1 phase]] to the [[S phase]] of the cell cycle.

== Function ==
CDK4 is a catalytic subunit of the protein kinase complex that is important for cell cycle [[G1 phase]] progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits [[D-type cyclins]] and, in an inhibitory manner, by [[p16^INK4a]]. It is crucial for the [[cell cycle]] progression at the G1 phase to ensure successful DNA replication. Activation of CDK4 leads to phosphorylation of target proteins, which in turn drives the cell from the G1 into the S phase.

== Structure ==
The CDK4 protein is composed of an ATP-binding region, a regulatory serine/threonine protein kinase domain, and a site for cyclin binding. The structure of CDK4 is similar to that of other members of the cyclin-dependent kinase family, with a small N-terminal domain and a larger C-terminal domain. The active site of CDK4, where ATP binding and phosphorylation occur, is located between these two domains.

== Clinical Significance ==
Alterations in the ''CDK4'' gene, such as amplification, overexpression, or mutation, have been implicated in the development of various [[cancer]]s, including [[melanoma]], [[breast cancer]], and [[glioblastoma]]. CDK4, along with [[CDK6]], is targeted by several [[inhibitor]]s, which are currently being investigated in clinical trials for cancer treatment. These inhibitors work by preventing the kinase activity of CDK4, thus halting the cell cycle progression and proliferation of cancer cells.

== CDK4 Inhibitors ==
Several small molecule inhibitors targeting CDK4 have been developed for the treatment of cancer. These inhibitors specifically bind to CDK4, preventing its association with D-type cyclins and thereby inhibiting its kinase activity. This results in cell cycle arrest at the G1 phase, leading to inhibition of cancer cell proliferation. Some of these inhibitors have shown promising results in clinical trials for various types of cancer.

== See Also ==
* [[Cyclin D]]
* [[Cyclin-dependent kinase inhibitor protein]]
* [[Cell cycle checkpoint]]
* [[Cancer therapy]]

[[Category:Cell cycle]]
[[Category:Enzymes]]
[[Category:Genes on human chromosome 12]]
{{medicine-stub}}

Cyclin-dependent kinase 4 - Revision history

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