regulation of mitotic spindle organization
Definition
Target type: biologicalprocess
Any process that modulates the rate, frequency or extent of the assembly, arrangement of constituent parts, or disassembly of the microtubule spindle during a mitotic cell cycle. [GOC:ascb_2009, GOC:dph, GOC:tb]
The regulation of mitotic spindle organization is a complex and tightly controlled process essential for accurate chromosome segregation during cell division. It involves a delicate interplay of various molecular components, including microtubules, motor proteins, and regulatory proteins.
**Microtubule Dynamics:**
* **Microtubule Polymerization and Depolymerization:** The mitotic spindle is composed of microtubules, dynamic polymers of tubulin subunits. Microtubule polymerization and depolymerization are tightly regulated during spindle assembly and function. Microtubule-associated proteins (MAPs) play crucial roles in regulating these processes, influencing the stability and dynamics of microtubules.
* **Microtubule Nucleation:** The formation of new microtubules is initiated at specialized structures called microtubule organizing centers (MTOCs), primarily the centrosomes in animal cells. The centrosomes contain γ-tubulin ring complexes (γ-TuRCs) that serve as nucleation sites for microtubule polymerization.
* **Microtubule Dynamics and Spindle Formation:** During prophase, microtubules emanating from the centrosomes grow and search for and attach to chromosomes. This process, known as microtubule capture, is essential for bipolar spindle formation.
**Motor Proteins:**
* **Kinesins and Dyneins:** Motor proteins, such as kinesins and dyneins, play critical roles in spindle assembly and chromosome segregation. They use ATP hydrolysis to generate movement along microtubules.
* **Kinesins:** Kinesins are involved in microtubule sliding, poleward movement of chromosomes, and spindle pole separation. Different kinesin families exhibit distinct functions in spindle assembly and function.
* **Dyneins:** Dyneins are involved in the inward movement of chromosomes and contribute to spindle pole focusing.
**Regulatory Proteins:**
* **Checkpoint Proteins:** Checkpoint proteins ensure the proper attachment of chromosomes to the spindle before the onset of anaphase. They monitor spindle assembly and chromosome alignment and delay cell cycle progression if errors are detected.
* **Cyclin-Dependent Kinases (CDKs):** CDKs play key roles in regulating spindle assembly and function. They activate specific proteins involved in microtubule dynamics, motor protein activity, and checkpoint control.
* **Other Regulatory Proteins:** Various other proteins, including Ran GTPase, Aurora kinases, and Polo kinases, are involved in regulating spindle assembly, chromosome segregation, and checkpoint control.
**Spindle Assembly and Function:**
* **Bipolar Spindle Formation:** Through microtubule capture and motor protein activity, a bipolar spindle is formed with two poles, each containing a centrosome.
* **Chromosome Alignment:** Chromosomes attach to microtubules via the kinetochore, a specialized protein complex on the centromere. Kinetochore microtubules attach to sister chromatids from opposite spindle poles, ensuring their proper alignment at the metaphase plate.
* **Chromosome Segregation:** During anaphase, sister chromatids are pulled apart by the shortening of kinetochore microtubules and the action of motor proteins. This process segregates chromosomes to opposite poles, ensuring the correct distribution of genetic material to daughter cells.
**Spindle Disassembly and Cytokinesis:**
* **Microtubule Depolymerization:** After chromosome segregation, the spindle microtubules depolymerize. This process is regulated by specific protein kinases and phosphatases.
* **Cytokinesis:** Following spindle disassembly, cytokinesis occurs, dividing the cytoplasm and creating two daughter cells.
**Regulation and Errors:**
* **Regulation:** The regulation of mitotic spindle organization is tightly controlled by a complex network of signaling pathways and protein interactions.
* **Errors:** Errors in spindle assembly or chromosome segregation can lead to aneuploidy, a condition characterized by an abnormal number of chromosomes. Aneuploidy is associated with various human diseases, including cancer.
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Proteins (2)
| Protein | Definition | Taxonomy |
|---|---|---|
| Protein mono-ADP-ribosyltransferase PARP3 | A protein mono-ADP-ribosyltransferase PARP3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y6F1] | Homo sapiens (human) |
| Targeting protein for Xklp2 | A targeting protein for Xklp2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9ULW0] | Homo sapiens (human) |
Compounds (16)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| pj-34 | PJ34 : A member of the class of phenanthridines that is 5,6-dihydrophenanthridine substituted at positions 2 and 6 by (N,N-dimethylglycyl)amino and oxo groups, respectively. It is a potent inhibitor of poly(ADP-ribose) polymerases PARP1 and PARP2 (IC50 of 110 nM and 86 nM, respectively) and exhibits anti-cancer, cardioprotective and neuroprotective properties. | phenanthridines; secondary carboxamide; tertiary amino compound | angiogenesis inhibitor; anti-inflammatory agent; antiatherosclerotic agent; antineoplastic agent; apoptosis inducer; cardioprotective agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; neuroprotective agent |
| 3-aminobenzoic acid | 3-aminobenzoic acid : An aminobenzoic acid carrying an amino group at position 3. 3-aminobenzoic acid: RN given refers to parent cpd | aminobenzoic acid | |
| 4-Methoxybenzamide | benzamides | ||
| rucaparib | AG14447: Poly(ADP-ribose) polymerase inhibitor; structure in first source | azepinoindole; caprolactams; organofluorine compound; secondary amino compound | antineoplastic agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| latonduine a | latonduine A: structure in first source | ||
| veliparib | benzimidazoles | EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor | |
| tak-901 | |||
| olaparib | cyclopropanes; monofluorobenzenes; N-acylpiperazine; phthalazines | antineoplastic agent; apoptosis inducer; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor | |
| mk 5108 | aromatic ether | ||
| mln 8237 | MLN 8237: an aurora kinase A inhibitor | benzazepine | |
| niraparib | 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide : A member of the class of indazoles that is 2H-indazole substituted by 4-(piperidin-3-yl)phenyl and aminocarbonyl groups at positions 2 and 7, respectively. It is a potent PARP1 inhibitor with IC50 of 3.2 nM. | benzenes; indazoles; piperidines; primary carboxamide | antineoplastic agent; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor |
| niraparib | niraparib : A 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide that has S-configuration. It is a potent inhibitor of PARP1 and PARP2 (IC50 of 3.8 and 2.1 nM, respectively) and approved as a first-line maintenance treatment for women with advanced ovarian cancer after responding to platinum-based chemotherapy. niraparib: structure in first source | 2-[4-(piperidin-3-yl)phenyl]-2H-indazole-7-carboxamide | antineoplastic agent; apoptosis inducer; EC 2.4.2.30 (NAD(+) ADP-ribosyltransferase) inhibitor; radiosensitizing agent |
| gsk 1070916 | GSK 1070916: an antineoplastic agent with aurora B/C kinase inhibitory activity | pyrazoles; ring assembly | |
| xav939 | XAV939 : A thiopyranopyrimidine in which a 7,8-dihydro-5H-thiopyrano[4,3-d]pyrimidine skeleton is substituted at C-4 by a hydroxy group and at C-2 by a para-(trifluoromethyl)phenyl group. XAV939: selectively inhibits beta-catenin-mediated transcription; structure in first source | (trifluoromethyl)benzenes; thiopyranopyrimidine | tankyrase inhibitor |
| bmn 673 | talazoparib: inhibits both PARP1 and PARP2; structure in first source | ||
| me0328 | ME0328: inhibits ARTD3; structure in first source |