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XB-ART-37349
J Cell Biol March 10, 2008; 180 (5): 867-75.

Cdk11 is a RanGTP-dependent microtubule stabilization factor that regulates spindle assembly rate.

Yokoyama H , Gruss OJ , Rybina S , Caudron M , Schelder M , Wilm M , Mattaj IW , Karsenti E .


Abstract
Production of Ran-guanosine triphosphate (GTP) around chromosomes induces local nucleation and plus end stabilization of microtubules (MTs). The nuclear protein TPX2 is required for RanGTP-dependent MT nucleation. To find the MT stabilizer, we affinity purify nuclear localization signal (NLS)-containing proteins from Xenopus laevis egg extracts. This NLS protein fraction contains the MT stabilization activity. After further purification, we used mass spectrometry to identify proteins in active fractions, including cyclin-dependent kinase 11 (Cdk11). Cdk11 localizes on spindle poles and MTs in Xenopus culture cells and egg extracts. Recombinant Cdk11 demonstrates RanGTP-dependent MT stabilization activity, whereas a kinase-dead mutant does not. Inactivation of Cdk11 in egg extracts blocks RanGTP-dependent MT stabilization and dramatically decreases the spindle assembly rate. Simultaneous depletion of TPX2 completely inhibits centrosome-dependent spindle assembly. Our results indicate that Cdk11 is responsible for RanGTP-dependent MT stabilization around chromosomes and that this local stabilization is essential for normal rates of spindle assembly and spindle function.

PubMed ID: 18316407
PMC ID: PMC2265385
Article link: J Cell Biol


Species referenced: Xenopus laevis
Genes referenced: cdk11b cdk19 dkc1 herpud1 nop56 nop58 npm1 ran tpx2


Article Images: [+] show captions
References [+] :
Bastiaens, Gradients in the self-organization of the mitotic spindle. 2006, Pubmed, Xenbase