title: FBXL5 interacts with p150Glued and regulates its ubiquitination.
abstract: 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.
authors.affiliation: Division of Cellular Dynamics, Hefei National Laboratory for Physical Sciences and Chinese University of Science & Technology, Hefei 230027, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Ding
authors.forename: Felix
authors.initials: F
authors.lastname: Aikhionbare
authors.forename: Changjiang
authors.initials: C
authors.lastname: Jin
authors.forename: Xuebiao
authors.initials: X
authors.lastname: Yao
mesh_terms: 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*
chemical_list: 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