Mitotic Spindle Regulation Pathway

Preferred Label : Mitotic Spindle Regulation Pathway;

NCIt related terms : Role of Ran in mitotic spindle regulation;

Alternative definition : BIOCARTA: One of the central features of mitotic cell division is the formation of the spindle that segregates chromosomes into each daughter cell. Chromosomes are not just passengers along for a ride with the spindle, but active participants in the nucleation and stabilization of spindle microtubules in their near vicinity. The ras-like GTPase Ran that regulates nucleocytoplasmic transport through the nuclear pore complex (NPC) during interphase also regulates the formation of the mitotic spindle. Ran plays a similar role in each of these processes, regulating downstream signaling pathways in a differential manner based on whether GDP or GTP is bound. Like other GTPases, the inherent GTPase activity of Ran is regulated by GTPase activating proteins (GAPs) and by exchange factors. An exchange factor that stimulates nucleotide exchange by the Ran GTPase is RCC1, which binds to chromatin in both interphase and mitosis. While RCC1 helps RAN drive transport between the nucleus and cytoplasm during interphase, the localization of RCC1 on chromatin during mitosis localizes Ran-GTP near chromosomes, localizing microtubule formation in these regions. Ran-BP1 and Ran-GAP1 stimulate GTP hydrolysis by Ran, converting it back to Ran-GDP further away from chromosomes. Aster promoting activities (APA) and the importin-alpha and importin-beta proteins involved with Ran in nucleocytoplasmic transport are also involved in mitotic spindle formation. Aster promoting activities stabilize microtubules during spindle formation, but binding of importins to APA neutralizes their activity in forming microtubules. The importins bind to APA when far from the chromosomes, where Ran-GDP predominates, but Ran-GTP near chromosomes causes importins to release APA factors including Tpx2 and NuMa, allowing them to stimulate microtubule formation. Tpx2 interacts with the microtubule motor protein Xklp2 and also activates the Aurora A mitotic kinase, required for spindle formation. In addition to regulating spindle formation, Ran may also help reform the nuclear envelope after cell division and may use a similar mechanism to regulate other cellular processes. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_ranMSpathway;

Details

Origin ID

C39213;

UMLS CUI

C1513355;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- Aurora Kinase A [NCIt concept]
- E3 SUMO-Protein Ligase RanBP2 [NCIt concept]
- GTP-Binding Nuclear Protein Ran [NCIt concept]
- Importin Subunit Beta-1 [NCIt concept]
- Kinesin-Like Protein KIF11 [NCIt concept]
- Nuclear Mitotic Apparatus Protein 1 [NCIt concept]
- Ran GTPase-Activating Protein 1 [NCIt concept]
- Structural Maintenance of Chromosomes Protein 3 [NCIt concept]
- Targeting Protein for Xklp2 [NCIt concept]
pathway_has_gene_element
- AURKA wt Allele [NCIt concept]
- KIF11 wt Allele [NCIt concept]
- KPNB1 wt Allele [NCIt concept]
- NUMA1 wt Allele [NCIt concept]
- RAN wt Allele [NCIt concept]
- RANBP2 wt Allele [NCIt concept]
- RANGAP1 wt Allele [NCIt concept]
- TPX2 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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