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)
| Protein | Definition | Taxonomy |
|---|---|---|
| Histone acetyltransferase KAT2B | A histone acetyltransferase KAT2B that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92831] | Homo sapiens (human) |
| Histone acetyltransferase KAT2A | A histone acetyltransferase KAT2A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q92830] | Homo sapiens (human) |
| Breast cancer type 1 susceptibility protein | A breast cancer type 1 susceptibility protein that is encoded in the genome of human. [PRO:DNx] | Homo sapiens (human) |
Compounds (14)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 4-aminophenol | 4-aminophenol : An amino phenol (one of the three possible isomers) which has the single amino substituent located para to the phenolic -OH group. 4-aminophenol: RN given refers to parent cpd | aminophenol | allergen; metabolite |
| embelin | embelin : A member of the class of dihydroxy-1,4-benzoquinones that is 2,5-dihydroxy-1,4-benzoquinone which is substituted by an undecyl group at position 3. Isolated from Lysimachia punctata and Embelia ribes, it exhibits antimicrobial, antineoplastic and inhibitory activity towards hepatitis C protease. embelin: from Embelia fruit (Myrsinaceae) | dihydroxy-1,4-benzoquinones | antimicrobial agent; antineoplastic agent; hepatitis C protease inhibitor; plant metabolite |
| beta-thujaplicin | beta-thujaplicin : A monoterpenoid that is cyclohepta-2,4,6-trien-1-one substituted by a hydroxy group at position 2 and an isopropyl group at position 4. Isolated from Thuja plicata and Chamaecyparis obtusa, it exhibits antimicrobial activities. beta-thujaplicin: structure | cyclic ketone; enol; monoterpenoid | antibacterial agent; antifungal agent; antineoplastic agent; antiplasmodial drug; plant metabolite |
| plumbagin | plumbagin : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone in which the hydrogens at positions 2 and 5 are substituted by methyl and hydroxy groups, respectively. plumbagin: a superoxide anion generator | hydroxy-1,4-naphthoquinone; phenols | anticoagulant; antineoplastic agent; immunological adjuvant; metabolite |
| ferrocin c | N-methyl-2-quinolone: structure in first source | ||
| epigallocatechin gallate | (-)-epigallocatechin 3-gallate : A gallate ester obtained by the formal condensation of gallic acid with the (3R)-hydroxy group of (-)-epigallocatechin. epigallocatechin gallate: a steroid 5alpha-reductase inhibitor and antimutagen in green tea (Camellia sinensis) | flavans; gallate ester; polyphenol | antineoplastic agent; antioxidant; apoptosis inducer; geroprotector; Hsp90 inhibitor; neuroprotective agent; plant metabolite |
| coenzyme a | adenosine 3',5'-bisphosphate | coenzyme; Escherichia coli metabolite; mouse metabolite | |
| anacardic acid | anacardic acid : A hydroxybenzoic acid that is salicylic acid substituted by a pentadecyl group at position 6. It is a major component of cashew nut shell liquid and exhibits an extensive range of bioactivities. anacardic acid: isolated from Anacardium occidentale; monophenol monooxygenase inhibitor | hydroxy monocarboxylic acid; hydroxybenzoic acid | anti-inflammatory agent; antibacterial agent; anticoronaviral agent; apoptosis inducer; EC 2.3.1.48 (histone acetyltransferase) inhibitor; EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor; neuroprotective agent; plant metabolite |
| 2-(3-Chloro-2-fluorophenyl)-2,3-dihydroisothiazol-3-one | organofluorine compound | ||
| guttiferone e | guttiferone E: isolated from the fruits of Garcinia pyrifera collected in Malaysia; structure in first source | ||
| 2-hydroxy-6-[(8Z,11Z)-pentadeca-8,11,14-trien-1-yl]benzoic acid | hydroxybenzoic acid | ||
| 3-furancarboxylic acid, tetrahydro-4-methylene-5-oxo-2-propyl-, (2r,3s)-rel- | gamma-lactone | ||
| i-bet726 | |||
| 1,2-bis(isothiazol-5-yl)disulfane | 1,2-bis(isothiazol-5-yl)disulfane: structure in first source |