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Molecular and Cellular Biology, May 2007, p. 3667-3681, Vol. 27, No. 10
0270-7306/07/$08.00+0     doi:10.1128/MCB.01386-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Functional Importance of the Anaphase-Promoting Complex-Cdh1-Mediated Degradation of TMAP/CKAP2 in Regulation of Spindle Function and Cytokinesis{triangledown} ,{dagger}

Kyung Uk Hong,1 Young Soo Park,1 Yeon-Sun Seong,2 Dongmin Kang,3 Chang-Dae Bae,1 and Joobae Park1*

Department of Molecular Cell Biology and Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon, Republic of Korea 440-746,1 Department of Biochemistry, Dankook University College of Medicine, San 29, Ansuh-dong, Cheonan, Chungnam, Republic of Korea 330-714,2 Korea Basic Science Institution, Chuncheon Branch, 192-1 Hyoja 2-dong, Chuncheon, Gangwon-do, Republic of Korea 200-7013

Received 28 July 2006/ Returned for modification 31 August 2006/ Accepted 16 February 2007

Cytoskeleton-associated protein 2 (CKAP2), also known as tumor-associated microtubule-associated protein (TMAP), is a novel microtubule-associated protein that is frequently upregulated in various malignances. However, its cellular functions remain unknown. A previous study has shown that its protein level begins to increase during G1/S and peaks at G2/M, after which it decreases abruptly. Ectopic overexpression of TMAP/CKAP2 induced microtubule bundling related to increased microtubule stability. TMAP/CKAP2 overexpression also resulted in cell cycle arrest during mitosis due to a defect in centrosome separation and subsequent formation of a monopolar spindle. We also show that degradation of TMAP/CKAP2 during mitotic exit is mediated by the anaphase-promoting complex bound to Cdh1 and that the KEN box motif near the N terminus is necessary for its destruction. Compared to the wild type, expression of a nondegradable mutant of TMAP/CKAP2 significantly increased the occurrence of spindle defects and cytokinesis failure. These results suggest that TMAP/CKAP2 plays a role in the assembly and maintenance of mitotic spindles, presumably by regulating microtubule dynamics, and its destruction during mitotic exit serves an important role in the completion of cytokinesis and in the maintenance of spindle bipolarity in the next mitosis.

* Corresponding author. Mailing address: Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, 300 Chunchundong, Jangangu, Suwon, Republic of Korea 440-746. Phone: 82 31 299 6130. Fax: 82 31 299 6149. E-mail: jbpark{at}med.skku.ac.kr

{triangledown} Published ahead of print on 5 March 2007.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, May 2007, p. 3667-3681, Vol. 27, No. 10
0270-7306/07/$08.00+0     doi:10.1128/MCB.01386-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hong, K. U., Kim, H.-J., Kim, H.-S., Seong, Y.-S., Hong, K.-M., Bae, C.-D., Park, J. (2009). Cdk1-Cyclin B1-mediated Phosphorylation of Tumor-associated Microtubule-associated Protein/Cytoskeleton-associated Protein 2 in Mitosis. J. Biol. Chem. 284: 16501-16512 [Abstract] [Full Text]  


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