Page last updated: 2024-10-24

negative regulation of centrosome duplication

Definition

Target type: biologicalprocess

Any process that decreases the frequency, rate or extent of centrosome duplication. Centrosome duplication is the replication of a centrosome, a structure comprised of a pair of centrioles and peri-centriolar material from which a microtubule spindle apparatus is organized. [GOC:dph, GOC:tb]

Negative regulation of centrosome duplication is a complex process that ensures accurate chromosome segregation during cell division. This process involves a delicate balance of proteins and signaling pathways that control the timing and number of centrosome duplications. Here is a detailed description of the biological process:

**1. Centrosome Licensing:**
* Prior to S phase, the centrosome licensing factor, CDK2, is active and allows the centrosome to become competent for duplication.
* This licensing step is essential to prevent premature duplication.

**2. G1/S Transition:**
* During the transition from G1 to S phase, CDK2 activity decreases, and CDK2 is replaced by CDK2-cyclin E complex.
* The activation of CDK2-cyclin E triggers the initiation of centrosome duplication.

**3. Centrosome Duplication:**
* Centrosome duplication involves the formation of a new centriole next to the existing one.
* The process is mediated by the recruitment and activation of a number of proteins, including PLK1, AURKA, and SAS6.
* These proteins play critical roles in centriole assembly and elongation.

**4. Centrosome Separation:**
* After duplication, the two centrosomes remain connected by microtubules and associated proteins.
* During mitosis, the centrosomes separate and migrate to opposite poles of the cell.
* This separation is facilitated by the action of motor proteins, including dynein and kinesin.

**5. Negative Regulation:**
* The process of centrosome duplication is tightly regulated to ensure that only one duplication event occurs per cell cycle.
* This negative regulation is achieved by a variety of mechanisms, including:
* **Phosphorylation:** Phosphorylation events by kinases, such as PLK1 and AURKA, regulate the activity of centrosome duplication proteins.
* **Ubiquitination:** Ubiquitination, a process that targets proteins for degradation, is crucial for controlling the levels of centrosome duplication proteins.
* **Checkpoint Mechanisms:** Checkpoint pathways, such as the spindle assembly checkpoint, ensure that centrosome duplication and chromosome segregation are properly coordinated.
* **Feedback Inhibition:** Once a centrosome has duplicated, it can inhibit the duplication of other centrosomes through feedback mechanisms.

**6. Errors in Centrosome Duplication:**
* Errors in centrosome duplication can lead to abnormal numbers of centrosomes in cells.
* This can result in aneuploidy (abnormal chromosome numbers), which can contribute to cancer development.
* Additionally, abnormal centrosome numbers can disrupt cell division and lead to other cellular defects.

**Overall, negative regulation of centrosome duplication is essential for maintaining genomic stability and proper cell division. The intricate interplay of proteins, signaling pathways, and checkpoint mechanisms ensures that centrosomes duplicate only once per cell cycle, contributing to the accurate segregation of chromosomes and the overall health of the organism.**'
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Proteins (1)

ProteinDefinitionTaxonomy
NucleophosminA nucleophosmin that is encoded in the genome of human. [PRO:DNx, UniProtKB:P06748]Homo sapiens (human)

Compounds (6)

CompoundDefinitionClassesRoles
imatinibaromatic amine;
benzamides;
N-methylpiperazine;
pyridines;
pyrimidines
antineoplastic agent;
apoptosis inducer;
tyrosine kinase inhibitor
pd 173955PD 173955: inhibits src family-selective tyrosine kinase; structure in first sourcearyl sulfide;
dichlorobenzene;
methyl sulfide;
pyridopyrimidine
tyrosine kinase inhibitor
ellagic acidcatechols;
cyclic ketone;
lactone;
organic heterotetracyclic compound;
polyphenol
antioxidant;
EC 1.14.18.1 (tyrosinase) inhibitor;
EC 2.3.1.5 (arylamine N-acetyltransferase) inhibitor;
EC 2.4.1.1 (glycogen phosphorylase) inhibitor;
EC 2.5.1.18 (glutathione transferase) inhibitor;
EC 2.7.1.127 (inositol-trisphosphate 3-kinase) inhibitor;
EC 2.7.1.151 (inositol-polyphosphate multikinase) inhibitor;
EC 2.7.4.6 (nucleoside-diphosphate kinase) inhibitor;
EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor;
EC 5.99.1.2 (DNA topoisomerase) inhibitor;
EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor;
food additive;
fungal metabolite;
geroprotector;
plant metabolite;
skin lightening agent
bosutinib4-((2,4-dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methyl-1-piperazinyl)propoxy)-3-quinolinecarbonitrile: a Src kinase inhibitor; structure in first sourceaminoquinoline;
aromatic ether;
dichlorobenzene;
N-methylpiperazine;
nitrile;
tertiary amino compound
antineoplastic agent;
tyrosine kinase inhibitor
crizotinibcrizotinib : A 3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amine that has R configuration at the chiral centre. The active enantiomer, it acts as a kinase inhibitor and is used for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Crizotinib: A piperidine and aminopyridine derivative that acts as an inhibitor of RECEPTOR PROTEIN-TYROSINE KINASES, including ANAPLASTIC LYMPHOMA KINASE (ALK) and HEPATOCYTE GROWTH FACTOR RECEPTOR (HGFR; c-Met). It is used in the treatment of NON-SMALL CELL LUNG CANCER.
3-[1-(2,6-dichloro-3-fluorophenyl)ethoxy]-5-[1-(piperidin-4-yl)pyrazol-4-yl]pyridin-2-amineantineoplastic agent;
biomarker;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor
ceritinibceritinib : A member of the class of aminopyrimidines that is 2,6-diamino-5-chloropyrimidine in which the amino groups at positions 2 and 6 are respectively carrying 2-methoxy-4-(piperidin-4-yl)-5-methylphenyl and 2-(isopropylsulfonyl)phenyl substituents. Used for the treatment of ALK-positive metastatic non-small cell lung cancer.

ceritinib: an anaplastic lymphoma kinase inhibitor
aminopyrimidine;
aromatic ether;
organochlorine compound;
piperidines;
secondary amino compound;
sulfone
antineoplastic agent;
EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor