FBXL5 interacts with p150Glued and regulates its ubiquitination.
The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. p150(Glued) is the dynactin subunit responsible for binding to dynein and microtubules. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which governs phosphorylation-dependent ubiquitination and subsequent proteolysis. Our recent study showed that the proteolysis of mitotic kinesin CENP-E is mediated by SCF via a direct Skp1 link [D. Liu, N. Zhang, J. Du, X. Cai, M. Zhu, C. Jin, Z. Dou, C. Feng, Y. Yang, L. Liu, K. Takeyasu, W. Xie, X. Yao, Interaction of Skp1 with CENP-E at the midbody is essential for cytokinesis, Biochem. Biophys. Res. Commun. 345 (2006) 394-402]. Here we show that F-box protein FBXL5 interacts with p150(Glued) and orchestrates its turnover via ubiquitination. FBXL5 binds to p150(Glued)in vitro and in vivo. FBXL5 and p150(Glued) co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150(Glued) and protein turnover of p150(Glued). Our findings provide a potential mechanism by which p150(Glued) protein function is regulated by SCFs.
Zhang
Ning
N
Division of Cellular Dynamics, Hefei National Laboratory for Physical Sciences and Chinese University of Science & Technology, Hefei 230027, China.
Liu
Jing
J
Ding
Xia
X
Aikhionbare
Felix
F
Jin
Changjiang
C
Yao
Xuebiao
X
D001665:Binding Sites; D002460:Cell Line; D000072159:Dynactin Complex; D044783:F-Box Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014452:Ubiquitins / Q000378:metabolism*
C000606360:DCTN1 protein, human; D000072159:Dynactin Complex; D044783:F-Box Proteins; C521741:FBXL5 protein, human; D008869:Microtubule-Associated Proteins; D014452:Ubiquitins; D043743:Ubiquitin-Protein Ligase Complexes; D044767:Ubiquitin-Protein Ligases