Cdk11 is a RanGTP-dependent Microtubule Stabilization Factor That Regulates Spindle Assembly Rate

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2008 Mar 5

PMID 18316407

Citations 40

Authors

Hideki Yokoyama

Oliver J Gruss

Sofia Rybina

Maiwen Caudron

Malgorzata Schelder

Matthias Wilm

Iain W Mattaj

Eric Karsenti

Affiliations

Soon will be listed here.

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.

Citing Articles

Unveiling the Movement of RanBP1 During the Cell Cycle and Its Interaction with a Cyclin-Dependent Kinase (CDK) in Plants.

Thome V, Ferreira P, Lubini G, Nogueira F, Strini E, Pinoti V Int J Mol Sci. 2025; 26(1.

PMID: 39795905 PMC: 11720235. DOI: 10.3390/ijms26010046.

Cyclin-dependent kinases: Masters of the eukaryotic universe.

Pluta A, Studniarek C, Murphy S, Norbury C Wiley Interdiscip Rev RNA. 2023; :e1816.

PMID: 37718413 PMC: 10909489. DOI: 10.1002/wrna.1816.

Augmin is a Ran-regulated spindle assembly factor.

Kraus J, Travis S, King M, Petry S J Biol Chem. 2023; 299(6):104736.

PMID: 37086784 PMC: 10318467. DOI: 10.1016/j.jbc.2023.104736.

The large cytoplasmic volume of oocyte.

Kyogoku H, Kitajima T J Reprod Dev. 2022; 69(1):1-9.

PMID: 36436912 PMC: 9939283. DOI: 10.1262/jrd.2022-101.

Cell cycle regulation and hematologic malignancies.

Dai Y, Jin F, Wu W, Kumar S Blood Sci. 2022; 1(1):34-43.

PMID: 35402801 PMC: 8975093. DOI: 10.1097/BS9.0000000000000009.

References

Bastiaens P, Caudron M, Niethammer P, Karsenti E . Gradients in the self-organization of the mitotic spindle. Trends Cell Biol. 2006; 16(3):125-34. DOI: 10.1016/j.tcb.2006.01.005. View

Wilde A, Zheng Y . Stimulation of microtubule aster formation and spindle assembly by the small GTPase Ran. Science. 1999; 284(5418):1359-62. DOI: 10.1126/science.284.5418.1359. View

Kalab P, Pu R, Dasso M . The ran GTPase regulates mitotic spindle assembly. Curr Biol. 1999; 9(9):481-4. DOI: 10.1016/s0960-9822(99)80213-9. View

Glotzer M, Murray A, Kirschner M . Cyclin is degraded by the ubiquitin pathway. Nature. 1991; 349(6305):132-8. DOI: 10.1038/349132a0. View

Trembley J, Hu D, Hsu L, Yeung C, Slaughter C, Lahti J . PITSLRE p110 protein kinases associate with transcription complexes and affect their activity. J Biol Chem. 2001; 277(4):2589-96. DOI: 10.1074/jbc.M109755200. View

Hannak E, Heald R . Investigating mitotic spindle assembly and function in vitro using Xenopus laevis egg extracts. Nat Protoc. 2007; 1(5):2305-14. DOI: 10.1038/nprot.2006.396. View

Kalab P, Weis K, Heald R . Visualization of a Ran-GTP gradient in interphase and mitotic Xenopus egg extracts. Science. 2002; 295(5564):2452-6. DOI: 10.1126/science.1068798. View

Kalab P, Pralle A, Isacoff E, Heald R, Weis K . Analysis of a RanGTP-regulated gradient in mitotic somatic cells. Nature. 2006; 440(7084):697-701. DOI: 10.1038/nature04589. View

Berke J, Sgambato V, Zhu P, Lavoie B, Vincent M, Krause M . Dopamine and glutamate induce distinct striatal splice forms of Ania-6, an RNA polymerase II-associated cyclin. Neuron. 2001; 32(2):277-87. DOI: 10.1016/s0896-6273(01)00465-2. View

10.

Gruss O, Schatz C, Guarguaglini G, Kast J, Wilm M, Le Bot N . Ran induces spindle assembly by reversing the inhibitory effect of importin alpha on TPX2 activity. Cell. 2001; 104(1):83-93. DOI: 10.1016/s0092-8674(01)00193-3. View

11.

Shevchenko A, Wilm M, Vorm O, Mann M . Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal Chem. 1996; 68(5):850-8. DOI: 10.1021/ac950914h. View

12.

Guarguaglini G, Gruss O, Segref A, Karsenti E, Mattaj I . Generation of GTP-bound Ran by RCC1 is required for chromatin-induced mitotic spindle formation. Nature. 1999; 400(6740):178-81. DOI: 10.1038/22133. View

13.

Gruss O, Wittmann M, Yokoyama H, Pepperkok R, Kufer T, Sillje H . Chromosome-induced microtubule assembly mediated by TPX2 is required for spindle formation in HeLa cells. Nat Cell Biol. 2002; 4(11):871-9. DOI: 10.1038/ncb870. View

14.

Nachury M, Maresca T, Salmon W, Waterman-Storer C, Heald R, Weis K . Importin beta is a mitotic target of the small GTPase Ran in spindle assembly. Cell. 2001; 104(1):95-106. DOI: 10.1016/s0092-8674(01)00194-5. View

15.

Hu D, Valentine M, Kidd V, Lahti J . CDK11(p58) is required for the maintenance of sister chromatid cohesion. J Cell Sci. 2007; 120(Pt 14):2424-34. DOI: 10.1242/jcs.007963. View

16.

Wilde A, Lizarraga S, Zhang L, Wiese C, Gliksman N, Walczak C . Ran stimulates spindle assembly by altering microtubule dynamics and the balance of motor activities. Nat Cell Biol. 2001; 3(3):221-7. DOI: 10.1038/35060000. View

17.

Ohba T, Nakamura M, Nishitani H, Nishimoto T . Self-organization of microtubule asters induced in Xenopus egg extracts by GTP-bound Ran. Science. 1999; 284(5418):1356-8. DOI: 10.1126/science.284.5418.1356. View

18.

Zhang C, Hughes M, Clarke P . Ran-GTP stabilises microtubule asters and inhibits nuclear assembly in Xenopus egg extracts. J Cell Sci. 1999; 112 ( Pt 14):2453-61. DOI: 10.1242/jcs.112.14.2453. View

19.

Petretti C, Savoian M, Montembault E, Glover D, Prigent C, Giet R . The PITSLRE/CDK11p58 protein kinase promotes centrosome maturation and bipolar spindle formation. EMBO Rep. 2006; 7(4):418-24. PMC: 1456919. DOI: 10.1038/sj.embor.7400639. View

20.

Hu D, Mayeda A, Trembley J, Lahti J, Kidd V . CDK11 complexes promote pre-mRNA splicing. J Biol Chem. 2002; 278(10):8623-9. DOI: 10.1074/jbc.M210057200. View