FBXL5 interacts with p150 and regulates its ubiquitination

• Published in: Biochemical and biophysical research communications Vol. 359; no. 1; pp. 34 - 39
• Main Authors: Zhang, Ning, Liu, Jing, Ding, Xia, Aikhionbare, Felix, Jin, Changjiang, Yao, Xuebiao
• Format: Journal Article
• Language: English
• Published: United States 20.07.2007
• Subjects: 60 APPLIED LIFE SCIENCES; CYTOPLASM; HELA CELLS; IN VITRO; IN VIVO; LIGASES; MICROTUBULES; PHOSPHORYLATION; PROTEOLYSIS
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.05.068

The microtubule motor cytoplasmic dynein and its activator dynactin drive vesicular transport and mitotic spindle organization. p150 {sup 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 {sup Glued} and orchestrates its turnover via ubiquitination. FBXL5 binds to p150 {sup Glued} in vitro and in vivo. FBXL5 and p150 {sup Glued} co-localize primarily in the cytoplasm with peri-nuclear enrichment in HeLa cells. Overexpression of FBXL5 promotes poly-ubiquitination of p150 {sup Glued} and protein turnover of p150 {sup Glued} . Our findings provide a potential mechanism by which p150 {sup Glued} protein function is regulated by SCFs.