Regulation of CDK Activity: Mechanisms and Control
CDK activity is regulated by cyclin binding, phosphorylation, inhibitory proteins, and cyclin degradation, ensuring precise cell cycle control.
Cyclin Binding
Cyclin-
dependent kinases (CDKs) require the binding of a regulatory subunit known as a cyclin to become active
. This binding is crucial for the kinase activity,
as it induces conformational changes that allow the CDK to phosphorylate its substrates
. The presence of cyclins is tightly regulated throughout the cell cycle,
with different cyclins being expressed at specific phases to ensure proper cell cycle progression
.
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Phosphorylation
Phosphorylation is another critical mechanism for regulating CDK activity. CDKs undergo phosphorylation at specific sites,
which can either activate or inhibit their function
. This process is often mediated by cyclin-dependent kinase-activating kinases (CAKs), which phosphorylate CDKs to promote their activation. Additionally, inhibitory phosphorylation can prevent CDK activation,
ensuring that the cell cycle is tightly controlled and only progresses when conditions are favorable
.
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Inhibitory Proteins
CDK activity is also regulated by inhibitory proteins such as p21 and p27,
which belong to the Cip/Kip family
. These proteins bind to cyclin-CDK complexes,
preventing their activation and thus halting cell cycle progression
. This inhibition is particularly important in response to DNA damage or other stress signals, ensuring that cells do not divide under unfavorable conditions.
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Cyclin Degradation
The degradation of cyclins is a key mechanism for controlling CDK activity and ensuring the timely progression of the cell cycle
. Cyclins are targeted for degradation by the ubiquitin-proteasome pathway, which marks them for destruction and removal from the cell. This process is essential for the transition between different phases of the cell cycle, as it ensures that CDKs are only active when needed and that the cell cycle does not proceed prematurely.
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