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Aberrant centrosome organisation with ensuing alterations of microtubule nucleation capacity enables tumour cells to proliferate and invade despite increased genomic instability. CEP192 is a key factor in the initiation process of centrosome duplication and in the control of centrosome microtubule nucleation. However, regulatory means of CEP192 have remained unknown. Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192. Among these, CEP192 is specifically targeted for proteasomal degradation by FBXL13. Accordingly, induced FBXL13 expression downregulates centrosomal γ-tubulin and disrupts centrosomal microtubule arrays. In addition, depletion of FBXL13 induces high levels of CEP192 and γ-tubulin at the centrosomes with the consequence of defects in cell motility. Together, we characterise FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumour-promoting implications.

Original publication

DOI

10.15252/embr.201744799

Type

Journal article

Journal

EMBO Rep

Publication Date

03/2018

Volume

19

Keywords

CEP192, FBXL13, F‐box protein, centrosome, ubiquitin, Animals, Calcium-Binding Proteins, Cell Cycle Proteins, Cell Line, Cell Movement, Cell Proliferation, Centrosome, Chromosomal Proteins, Non-Histone, F-Box Proteins, Gene Expression Regulation, Genomic Instability, Homeostasis, Humans, Mice, Microtubules, Proteasome Endopeptidase Complex, SKP Cullin F-Box Protein Ligases, Tubulin, Ubiquitin-Protein Ligases