negative regulation of centriole replication

Definition

Target type: biologicalprocess

Any process that stops, prevents, or reduces the frequency, rate or extent of centriole replication. [GOC:ai]

Centriole replication, the process by which new centrioles are generated, is tightly regulated to ensure the proper number and arrangement of these essential microtubule-organizing centers. Negative regulation of centriole replication involves a complex interplay of molecular mechanisms that suppress the formation of excess centrioles. This regulation is crucial for maintaining genomic integrity and cellular function.

One key aspect of negative regulation is the control of the licensing factor, PLK4. PLK4, a protein kinase, is essential for initiating centriole duplication. Its activity is tightly regulated to ensure that only one new centriole is formed per existing centriole. Several mechanisms contribute to PLK4 regulation:

* **Phosphorylation:** PLK4 is phosphorylated by other kinases, such as Aurora A, which can modulate its activity and localization.
* **Protein interactions:** PLK4 interacts with several proteins that can inhibit its activity. These include CPAP and SAS-6, which are involved in centriole assembly.
* **Proteolysis:** PLK4 can be degraded by the proteasome, a cellular machinery responsible for protein degradation.

Another level of regulation involves the control of centriole assembly factors. These proteins are required for the formation of the new centriole structure. Their activity is tightly controlled by various mechanisms:

* **Post-translational modifications:** Proteins involved in centriole assembly, such as SAS-6, can be modified by ubiquitination or acetylation, which can regulate their function.
* **Localization:** Some centriole assembly factors, such as CPAP, are localized to specific regions of the centriole, limiting their activity.
* **Interactions:** Proteins involved in centriole assembly can interact with other proteins that inhibit their activity.

Finally, negative regulation also involves the control of the centriole cycle itself. The centriole cycle is a specific program of events that governs centriole duplication. This cycle ensures that centrioles are duplicated only once per cell cycle. The cycle is controlled by a complex interplay of proteins, including cyclin-dependent kinases (CDKs) and their regulators.

In summary, negative regulation of centriole replication involves multiple levels of control, including the regulation of key proteins, the control of centriole assembly factors, and the control of the centriole cycle itself. This intricate regulation ensures that centrioles are duplicated only when and where they are needed, maintaining genomic integrity and cellular function.'
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Proteins (3)

Compounds (14)