Browse > Article
http://dx.doi.org/10.14348/molcells.2019.0142

c-Cbl Acts as an E3 Ligase Against DDA3 for Spindle Dynamics and Centriole Duplication during Mitosis  

Gwon, Dasom (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University)
Hong, Jihee (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University)
Jang, Chang-Young (Drug Information Research Institute, College of Pharmacy, Sookmyung Women's University)
Publication Information
Molecules and Cells / v.42, no.12, 2019 , pp. 840-849 More about this Journal
Abstract
The spatiotemporal mitotic processes are controlled qualitatively by phosphorylation and qualitatively by ubiquitination. Although the SKP1-CUL1-F-box protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C) mainly mediate ubiquitin-dependent proteolysis of mitotic regulators, the E3 ligase for a large portion of mitotic proteins has yet to be identified. Here, we report c-Cbl as an E3 ligase that degrades DDA3, a protein involved in spindle dynamics. Depletion of c-Cbl led to increased DDA3 protein levels, resulting in increased recruitment of Kif2a to the mitotic spindle, a concomitant reduction in spindle formation, and chromosome alignment defects. Furthermore, c-Cbl depletion induced centrosome over-duplication and centriole amplification. Therefore, we concluded that c-Cbl controls spindle dynamics and centriole duplication through its E3 ligase activity against DDA3.
Keywords
c-Cbl; centriole; centrosome; DDA3; E3 ligase; spindle dynamics;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Nakayama, K.I. and Nakayama, K. (2006). Ubiquitin ligases: cell-cycle control and cancer. Nat. Rev. Cancer 6, 369-381.   DOI
2 Schmidt, M.H.H. and Dikic, I. (2005). The Cbl interactome and its functions. Nat. Rev. Mol. Cell Biol. 6, 907-918.   DOI
3 Shrestha, N., Shrestha, H., Ryu, T., Kim, H., Simkhada, S., Cho, Y.C., Park, S.Y., Cho, S., Lee, K.Y., Lee, J.H., et al. (2018). ${\delta}$-Catenin increases the stability of EGFR by decreasing c-Cbl interaction and enhances EGFR/Erk1/2 signaling in prostate cancer. Mol. Cells 41, 320-330.   DOI
4 Simunic, J. and Toilc, I.M. (2016). Mitotic spindle assembly: building the bridge between sister K-fibers. Trends Biochem. Sci. 41, 824-833.   DOI
5 Lee, H. (2014). How chromosome mis-segregation leads to cancer: lessons from BubR1 mouse models. Mol. Cells 37, 713-718.   DOI
6 Skaar, J.R. and Pagano, M. (2009). Control of cell growth by the SCF and APC/C ubiquitin ligases. Curr. Opin. Cell Biol. 21, 816-824.   DOI
7 Tsou, M.F., Wang, W.J., George, K.A., Uryu, K., Stearns, T., and Jallepalli, P.V. (2009). Polo kinase and separase regulate the mitotic licensing of centriole duplication in human cells. Dev. Cell 17, 344-354.   DOI
8 Uematsu, K., Okumura, F., Tonogai, S., Joo-Okumura, A., Alemayehu, D.H., Nishikimi, A., Fukui, Y., Nakatsukasa, K., and Kamura, T. (2016). ASB7 regulates spindle dynamics and genome integrity by targeting DDA3 for proteasomal degradation. J. Cell Biol. 215, 95-106.   DOI
9 Wong, J. and Fang, G.W. (2006). HURP controls spindle dynamics to promote proper interkinetochore tension and efficient kinetochore capture. J. Cell Biol. 173, 879-891.   DOI
10 Fang, G., Yu, H., and Kirschner, M.W. (1998). The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev. 12, 1871-1883.   DOI
11 Grovdal, L.M., Stang, E., Sorkin, A., and Madshus, I.H. (2004). Direct interaction of Cbl with pTyr 1045 of the EGF receptor (EGFR) is required to sort the EGFR to lysosomes for degradation. Exp. Cell Res. 300, 388-395.   DOI
12 Huang, B., Pei, H.Z., Chang, H.W., and Baek, S.H. (2018). The E3 ubiquitin ligase Trim13 regulates Nur77 stability via casein kinase $2{\alpha}$. Sci. Rep. 8, 13895.   DOI
13 Jin, J., Cardozo, T., Lovering, R.C., Elledge, S.J., Pagano, M., and Harper, J.W. (2004). Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev. 18, 2573-2580.   DOI
14 Hunter, S., Burton, E.A., Wu, S.C., and Anderson, S.M. (1999). Fyn associates with Cbl and phosphorylates tyrosine 731 in Cbl, a binding site for phosphatidylinositol 3-kinase. J. Biol. Chem. 274, 2097-2106.   DOI
15 Jang, C.Y., Wong, J., Coppinger, J.A., Seki, A., Yates, J.R., 3rd, and Fang, G.W. (2008). DDA3 recruits microtubule depolymerase Kif2a to spindle poles and controls spindle dynamics and mitotic chromosome movement. J. Cell Biol. 181, 255-267.   DOI
16 Jiang, X., Huang, F., Marusyk, A., and Sorkin, A. (2003). Grb2 regulates internalization of EGF receptors through clathrin-coated pits. Mol. Biol. Cell 14, 858-870.   DOI
17 Kline-Smith, S.L. and Walczak, C.E. (2004). Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics. Mol. Cell 15, 317-327.   DOI
18 Kwon, H.J., Park, J.E., Song, H., and Jang, C.Y. (2016). DDA3 and Mdp3 modulate Kif2a recruitment onto the mitotic spindle to control minus-end spindle dynamics. J. Cell Sci. 129, 2719-2725.   DOI
19 Meisner, H., Conway, B.R., Hartley, D., and Czech, M.P. (1995). Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells. Mol. Cell Biol. 15, 3571-3578.   DOI
20 Meraldi, P. and Nigg, E.A. (2002). The centrosome cycle. FEBS Lett. 521, 9-13.   DOI
21 Musacchio, A. and Salmon, E.D. (2007). The spindle-assembly checkpoint in space and time. Nat. Rev. Mol. Cell Biol. 8, 379-393.   DOI
22 Choi, Y.H., Han, Y., Lee, S.H., Jin, Y.H., Bahn, M., Hur, K.C., Yeo, C.Y., and Lee, K.Y. (2015). Cbl-b and c-Cbl negatively regulate osteoblast differentiation by enhancing ubiquitination and degradation of Osterix. Bone 75, 201-209.   DOI
23 Arquint, C. and Nigg, E.A. (2016). The PLK4-STIL-SAS-6 module at the core of centriole duplication. Biochem. Soc. Trans. 44, 1253-1263.   DOI
24 Castro, A., Bernis, C., Vigneron, S., Labbe, J.C., and Lorca, T. (2005). The anaphase-promoting complex: a key factor in the regulation of cell cycle. Oncogene 24, 314-325.   DOI
25 Cheeseman, I.M., Niessen, S., Anderson, S., Hyndman, F., Yates, J.R., 3rd, Oegema, K., and Desai, A. (2004). A conserved protein network controls assembly of the outer kinetochore and its ability to sustain tension. Genes Dev. 18, 2255-2268.   DOI
26 Dulic, V., Lees, E., and Reed, S.I. (1992). Association of human cyclin E with a periodic G1-S phase protein kinase. Science 257, 1958-1961.   DOI