FBXL13 regulates centrosome homeostasis and migration through ubiquitin- mediated proteolysis

Aberrant centrosome organization with ensuing alterations of microtubule nucleation enables tumor cells to proliferate and invade despite increased genomic instability. CEP192 is a key factors 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 degredation 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 corresponding to defects in cell motility. Together, we characterize FBXL13 as a novel regulator of microtubule nucleation activity and highlight a role in promoting cell motility with potential tumor-promoting implications.